Eicosanoid - AbsoluteAstronomy.com

In biochemistry, eicosanoids (preferred IUPAC name

Preferred IUPAC name

In chemical nomenclature, a preferred IUPAC name is a unique name, assigned to a chemical substance and preferred among the possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for choosing between multiple possibilities in situations where it...

icosanoids) are signaling molecules

Lipid signaling

Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses...

made by oxidation of twenty-carbon essential fatty acid

Essential fatty acid

Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them...

s, (EFAs).
They exert complex control over many bodily systems, mainly in inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

or immunity

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

, and as messengers in the central nervous system

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

.
The networks of controls that depend upon eicosanoids are among the most complex in the human body.

Eicosanoids derive from either omega-3

Omega-3 fatty acid

N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....

(ω-3) or omega-6

Omega-6 fatty acid

n−6 fatty acids are a family of unsaturated fatty acids that have in common a final carbon–carbon double bond in the n−6 position, that is, the sixth bond, counting from the methyl end.The biological effects of the n−6 fatty acids are largely mediated by their conversion to n-6 eicosanoids...

(ω-6) EFAs.
The ω-6 eicosanoids are generally pro-inflammatory; ω-3's are much less so.
The amounts and balance of these fats in a person's diet will affect the body's eicosanoid-controlled functions, with effects on cardiovascular disease

Cardiovascular disease

Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

, triglycerides, blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

, and arthritis

Arthritis

Arthritis is a form of joint disorder that involves inflammation of one or more joints....

. Anti-inflammatory drugs such as aspirin

Aspirin

Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

and other NSAIDs act by downregulating eicosanoid synthesis.

There are four families of eicosanoids—the prostaglandin

Prostaglandin

A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....

s, prostacyclin

Prostacyclin

Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...

s, the thromboxane

Thromboxane

Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring....

s and the leukotriene

Leukotriene

Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...

s. For each, there are two or three separate series, derived either from an ω-3 or ω-6 EFA. These series' different activities largely explain the health effects of ω-3 and ω-6 fats.

Nomenclature

See related detail at Essential Fatty Acid Interactions—Nomenclature

"Eicosanoid" (eicosa-, Greek

Greek language

Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...

for "twenty"; see icosahedron

Icosahedron

In geometry, an icosahedron is a regular polyhedron with 20 identical equilateral triangular faces, 30 edges and 12 vertices. It is one of the five Platonic solids....

) is the collective term for oxygenated derivatives of three different 20-carbon essential fatty acids:

Eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...

(EPA), an ω-3 fatty acid with 5 double bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...

s;
Arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

(AA), an ω-6 fatty acid, with 4 double bonds;
Dihomo-gamma-linolenic acid
Dihomo-gamma-linolenic acid
Dihomo-γ-linolenic acid is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 . DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product...

(DGLA), an ω-6, with 3 double bonds.

Current usage limits the term to the leukotriene

Leukotriene

s (LT) and three types of prostanoid

Prostanoid

Prostanoid is the term used to describe a subclass of eicosanoids consisting of: the prostaglandins , the thromboxanes and the prostacyclins - Biosynthesis : Cyclooxygenase catalyzes the conversion of the free essential fatty acids to...

s—prostaglandin

Prostaglandin

s (PG) prostacyclin

Prostacyclin

Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...

s (PGI), and thromboxane

Thromboxane

s (TX). This is the definition used in this article. However, several other classes can technically be termed eicosanoid, including the hepoxilin

Hepoxilin

Hepoxilins are nonclassic eicosanoid hormones involved in inflammation.-Biochemistry:They derive from arachidonic acid via oxidation by the enzyme 12-lipoxygenase...

s, resolvins

Resolvins

Resolvins are compounds that are made by the human body from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid . They are produced by the COX-2 pathway especially in the presence of aspirin...

, isofuran

Isofuran

Isofurans are nonclassic eicosanoids formed nonenzymatically by free radical mediated peroxidation of arachidonic acid. The isofurans are similar to the isoprostanes and are formed under similar conditions, but contain a substituted tetrahydrofuran ring...

s, isoprostane

Isoprostane

The isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidationof essential fatty acids without the direct action of cyclooxygenase enzyme....

s, lipoxin

Lipoxin

Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation....

s, epi-lipoxin

Epi-lipoxin

Epi-lipoxins are the 5R-epimers of lipoxins.These nonclassic eicosanoids are formed in vivo, in the presence of aspirin. They play a counter-regulatory role in inflammation, serving as a stop signal....

s, epoxyeicosatrienoic acid

Epoxyeicosatrienoic acid

The Epoxyeicosatrienoic acids or EETs are signaling molecules formed by the action of Cytochrome P450 epoxygenase on 20-carbon essential fatty acids, such as arachidonic acid, from which it is produced by the enzyme epoxygenase....

s (EETs) and endocannabinoids.
LTs and prostanoids are sometimes termed 'classic eicosanoids'
in contrast to the 'novel', 'eicosanoid-like' or 'nonclassic eicosanoid

Nonclassic eicosanoid

Nonclassic eicosanoids are biologically active signaling molecules made by oxygenation of twenty-carbon fatty acids other than the classic eicosanoids.-Terminology:"Eicosanoid" is the collective...

s'.

A particular eicosanoid is denoted by a four-character abbreviation, composed of:

Its two letter abbreviation (above),
One A-B-C sequence-letter; and
A subscript, indicating the number of double bonds
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

.

Examples are:

The EPA-derived prostanoids have three double bonds, (e.g. PGG₃, PGH₃, PGI₃, TXA₃) while its leukotrienes have five, (LTB₅).
The AA-derived prostanoids have two double bonds, (e.g. PGG₂, PGH₂, PGI₂, TXA₂) while its leukotrienes have four, (LTB₄).

Furthermore, stereochemistry

Stereochemistry

Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....

may differ among the pathways, indicated by Greek letters, e.g. for (PGF_2α).

Biosynthesis

Two families of enzymes catalyze fatty acid oxygenation to produce the eicosanoids:

Cyclooxygenase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...

, or COX, generates the prostanoids.
Lipoxygenase
Lipoxygenase
Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:...

, or LOX, in several forms. 5-lipoxygenase (5-LO) generates the leukotrienes.

Eicosanoids are not stored within cells, but are synthesized

Biosynthesis

Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

as required.
They derive from the fatty acids that make up the cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

and nuclear membrane

Nuclear envelope

A nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...

.

Eicosanoid biosynthesis begins when cell is activated by mechanical trauma, cytokines, growth factors or other stimuli.
(The stimulus may even be an eicosanoid from a neighboring cell; the pathways are complex.) This triggers the release of a phospholipase

Phospholipase

A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...

at the cell membrane

Cell membrane

.
The phospholipase travels to the nuclear membrane.
There, the phospholipase catalyzes ester hydrolysis

Hydrolysis

Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

of phospholipid (by A₂

Phospholipase A2

Phospholipases A2 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids...

) or diacylglycerol (by phospholipase C

Phospholipase C

Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...

).
This frees a 20-carbon essential fatty acid

Essential fatty acid

Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them...

. This hydrolysis appears to be the rate-determining step

Rate-determining step

The rate-determining step is a chemistry term for the slowest step in a chemical reaction. The rate-determining step is often compared to the neck of a funnel; the rate at which water flows through the funnel is determined by the width of the neck, not by the speed at which water is poured in. In...

for eicosanoid formation.

The fatty acids may be released by any of several phospholipases.
Of these, type IV cytosolic phospholipase A₂ (cPLA₂) is the key actor, as cells lacking cPLA₂ are generally devoid of eicosanoid synthesis. The phospholipase
cPLA₂ is specific for phospholipids that contain AA, EPA or GPLA at the SN2

Phospholipase A2

position.
Interestingly, cPLA₂ may also release the lysophospholipid that becomes platelet-activating factor

Platelet-activating factor

Platelet-activating factor, also known as a PAF, PAF-acether or AGEPC is a potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation and degranulation, inflammation, and anaphylaxis...

Peroxidation and reactive oxygen species

Next, the free fatty acid is oxygenated along any of several pathways; see the Pathways table. The eicosanoid pathways (via lipoxygenase

Lipoxygenase

Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:...

or COX

Cyclooxygenase

Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...

) add molecular oxygen

Oxygen

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

(O₂). Although the fatty acid is symmetric

Symmetry

Symmetry generally conveys two primary meanings. The first is an imprecise sense of harmonious or aesthetically pleasing proportionality and balance; such that it reflects beauty or perfection...

, the resulting eicosanoids are chiral

Chirality (chemistry)

A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

; the oxidation proceeds with high stereospecificity

Stereospecificity

In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one of the stereoisomers."Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline...

.

The oxidation of lipids is hazardous to cells, particularly when close to the nucleus.
There are elaborate mechanisms to prevent unwanted oxidation.
COX, the lipoxygenases and the phospholipases are tightly controlled—there are at least eight proteins activated to coordinate generation of leukotrienes.
Several of these exist in multiple isoforms.

Oxidation by either COX or lipoxygenase releases reactive oxygen species

Reactive oxygen species

Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

(ROS) and the initial products in eicosanoid generation are themselves highly reactive peroxide

Peroxide

A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...

s.
LTA₄ can form adduct

Adduct

An adduct is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components. The resultant is considered a distinct molecular species...

s with tissue DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

.
Other reactions of lipoxygenases generate cellular damage; murine

Murinae

The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. This subfamily is larger than all mammal families except the Cricetidae and Muridae, and is larger than all mammal orders except the bats and the remainder of the...

models implicate 15-lipoxygenase in the pathogenesis

Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

of atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

.
The oxidation in eicosanoid generation is compartmentalized; this limits the peroxides' damage.
The enzymes which are biosynthetic for eicosanoids (e.g. glutathione-S-transferases

Transferase

In biochemistry, a transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another . For example, an enzyme that catalyzed this reaction would be a transferase:In this example, A would be the donor, and B would be the acceptor...

, epoxide hydrolase

Hydrolase

In biochemistry, a hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. For example, an enzyme that catalyzed the following reaction is a hydrolase:-Nomenclature:...

s and carrier protein

Carrier protein

Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...

s) belong to families whose functions are largely involved with cellular detoxification.
This suggests that eicosanoid signaling may have evolved from the detoxification of ROS.

The cell must realize some benefit from generating lipid hydroperoxides close-by its nucleus.
PGs and LTs may signal or regulate DNA-transcription

Transcription (genetics)

Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

there;
LTB₄ is ligand for PPARα

Peroxisome proliferator-activated receptor

In the field of molecular biology, the peroxisome proliferator-activated receptors are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes...

.
(See diagram at PPAR

Peroxisome proliferator-activated receptor

**Structures of Selected Eicosanoids**

Prostaglandin E₁. The 5-member ring is characteristic of the class.	Thromboxane A₂. Oxygens have moved into the ring.		Leukotriene B₄. Note the 3 conjugated double bonds.

Prostacyclin I₂. The second ring distinguishes it from the prostaglandins.		Leukotriene E₄, an example of a cysteinyl leukotriene.

Prostanoid pathways

See Prostanoid#Biosynthesis.

Cyclooxygenase

(COX) catalyzes the conversion of the free essential fatty acids to prostanoids by a two-step process.
First, two molecules of O₂ are added as two peroxide linkages, and a 5-member carbon ring is forged near the middle of the fatty acid chain. This forms the short-lived, unstable intermediate Prostaglandin G (PGG).
Next, one of the peroxide linkages sheds a single oxygen, forming PGH. (See diagrams and more detail of these steps at Cyclooxygenase

Cyclooxygenase

).

All three classes of prostanoids originate from PGH.
All have distinctive rings in the center of the molecule.
They differ in their structures.
The PGH compounds (parents to all the rest) have a 5-carbon ring, bridged by two oxygens (a peroxide.) As the example in Structures of Selected Eicosanoids figure shows, the derived prostaglandins contain a single, unsaturated 5-carbon ring.
In prostacyclins, this ring is conjoined to another oxygen-containing ring.
In thromboxanes the ring becomes a 6-member ring with one oxygen. The leukotrienes do not have rings.
(See more detail, including the enzymes involved, in diagrams at Prostanoid

Prostanoid

.)

Several drugs lower inflammation by blocking prostanoid synthesis; see detail at Cyclooxygenase

Cyclooxygenase

, Aspirin

Aspirin

and NSAID

Non-steroidal anti-inflammatory drug

Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...

Leukotriene pathways

See Leukotriene#Biosynthesis.

The enzyme 5-lipoxygenase

Lipoxygenase

(5-LO) uses 5-lipoxygenase activating protein (FLAP) to convert arachidonic acid

Arachidonic acid

Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

into 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which spontaneously reduces

Redox

Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

to 5-hydroxyeicosatetraenoic acid

5-hydroxyeicosatetraenoic acid

5-Hydroxyeicosatetraenoic acid is an endogenous eicosanoid. 5-HETE is an intermediate in the pathway of leukotriene synthesis. In addition, it is a modulator of tubuloglomerular feedback.-See also:* 12-Hydroxyeicosatetraenoic acid...

(5-HETE). The enzyme LTA synthase acts on 5-HPETE to convert it into leukotriene

Leukotriene

A₄ (LTA₄), which may be converted into LTB₄ by the enzyme leukotriene A4 epoxide hydrolase. Eosinophils, mast cell

Mast cell

A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...

s, and alveolar macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s use the enzyme leukotriene C4 synthase to conjugate glutathione

Glutathione

Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

with LTA₄ to make LTC₄, which is transported outside the cell, where a glutamic acid

Glutamic acid

Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

moiety is removed from it to make LTD₄. The leukotriene LTD₄ is then cleaved by
dipeptidases to make LTE₄. The leukotrienes
LTC₄, LTD₄ and LTE₄ all contain cysteine

Cysteine

Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

and are collectively known as the cysteinyl leukotrienes.

Function and pharmacology

Metabolic actions of selected prostanoids and leukotrienes^†
PGD₂	Promotion of sleep	TXA₂	Stimulation of platelet aggregation; vasoconstriction
PGE₂	Smooth muscle contraction; inducing pain, heat, fever; bronchoconstriction Bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Bronchoconstriction can also be due to an accumulation of thick mucus....	15d-PGJ₂	Adipocyte Adipocyte However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult... differentiation
PGF_2α	Uterine contraction Contraction (childbirth) -Throughout menstrual cycle:The uterus frequently contracts throughout the entire menstrual cycle, and these contractions have been termed endometrial waves or contractile waves. These appear to involve only the sub-endometrial layer of the myometrium...	LTB₄	Leukocyte chemotaxis Chemotaxis Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
PGI₂	Inhibition of platelet aggregation; vasodilation; embryo implantation	Cysteinyl-LTs	Anaphylaxis; bronchial smooth muscle contraction.
^†Shown eicosanoids are AA-derived; EPA-derived generally have weaker activity

Eicosanoids exert complex control over many bodily systems, mainly in inflammation

Inflammation

or immunity

Immune system

, and as messengers in the central nervous system

Central nervous system

. They are found in most living things. In humans, eicosanoids are local hormone

Hormone

A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s that are released by most cells, act on that same cell or nearby cells (i.e., they are autocrine and paracrine mediators), and then are rapidly inactivated.

Eicosanoids have a short half-life, ranging from seconds to minutes. Dietary antioxidants inhibit the generation of some inflammatory eicosanoids, e.g. trans-resveratrol

Resveratrol

Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi....

against thromboxane and some leukotrienes.
Most eicosanoid receptors are members of the G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

superfamily; see the Receptors table or the article eicosanoid receptor

Eicosanoid receptor

An eicosanoid receptor is an integral membrane protein which detects the presence of eicosanoid signaling molecules. Most, though not all, are G protein-coupled receptors...

Receptors: There are specific receptors for all eicosanoids (see also: eicosanoid receptor
Eicosanoid receptor
An eicosanoid receptor is an integral membrane protein which detects the presence of eicosanoid signaling molecules. Most, though not all, are G protein-coupled receptors...

s)
Leukotrienes: CysLT1 (Cysteinyl leukotriene receptor type 1) CysLT2 (Cysteinyl leukotriene receptor type 2) BLT1 (Leukotriene B4 receptor)
Prostanoids: PGD₂: DP-(PGD₂) PGE₂: EP₁-(PGE₂) EP₂-(PGE₂) EP₃-(PGE₂) EP₄-(PGE₂) PGF_2α: FP-(PGF_2α) PGI₂ (prostacyclin): IP-(PGI₂) TXA₂ (thromboxane): TP-(TXA₂)

The ω-3 and ω-6 series

Arachidonic acid

(AA; 20:4 ω-6) sits at the head of the 'arachidonic acid cascade'—more than twenty different eicosanoid-mediated signaling paths controlling a wide array of cellular functions, especially those regulating inflammation

Inflammation

, immunity and the central nervous system

Central nervous system

.

In the inflammatory response, two other groups of dietary essential fatty acids form cascades that parallel and compete with the arachidonic acid cascade. EPA (20:5 ω-3)

Eicosapentaenoic acid

Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...

provides the most important competing cascade. DGLA (20:3 ω-6)

Dihomo-gamma-linolenic acid

Dihomo-γ-linolenic acid is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 . DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product...

provides a third, less prominent cascade. These two parallel cascades soften the inflammatory effects of AA and its products. Low dietary intake of these less-inflammatory essential fatty acids, especially the ω-3s, has been linked to several inflammation-related diseases, and perhaps some mental illness

Mental illness

A mental disorder or mental illness is a psychological or behavioral pattern generally associated with subjective distress or disability that occurs in an individual, and which is not a part of normal development or culture. Such a disorder may consist of a combination of affective, behavioural,...

es.

The U.S. National Institutes of Health

National Institutes of Health

The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

and the National Library of Medicine state that there is 'A' level evidence that increased dietary ω-3 improves outcomes in hypertriglyceridemia

Hypertriglyceridemia

In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...

, secondary cardiovascular disease

Cardiovascular disease

prevention and hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

.
There is 'B' level evidence ('good scientific evidence') for increased dietary ω-3 in primary prevention of cardiovascular disease, rheumatoid arthritis

Rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

and protection from ciclosporin toxicity

Ciclosporin

Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...

in organ transplant

Organ transplant

Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...

patients.
They also note more preliminary evidence showing that dietary ω-3 can ease symptoms in several psychiatric disorders.

Besides the influence on eicosanoids, dietary polyunsaturated fats modulate immune response through three other molecular mechanisms. They
(a) alter membrane composition and function

Membrane fluidity

In biology, the membrane fluidity refers to the viscosity of the lipid bilayer of a cell membrane.The membrane phospholipids incorporate fatty acids of varying length and saturation...

, including the composition of lipid raft

Lipid raft

The plasma membrane of cells is made of a combination of glycosphingolipids and protein receptors organized in glycolipoprotein microdomains termed lipid rafts...

s;
(b) change cytokine

Cytokine

Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

biosynthesis and (c) directly activate gene transcription. Of these, the action on eicosanoids is the best explored.

Mechanisms of ω-3 action

The eicosanoids from AA generally promote inflammation. Those from EPA and from GLA

Gamma-Linolenic acid

γ-Linolenic acid is a fatty acid found primarily in vegetable oils...

(via DGLA) are generally less inflammatory, or inactive, or even anti-inflammatory.
The figure shows the ω-3 and -6 synthesis chains, along with the major eicosanoids from AA, EPA and DGLA.

Dietary ω-3 and GLA counter the inflammatory effects of AA's eicosanoids in three ways, along the eicosanoid pathways:

Displacement—Dietary ω-3 decreases tissue concentrations of AA, so there is less to form ω-6 eicosanoids.
Competitive inhibition—DGLA and EPA compete with AA for access to the cyclooxygenase and lipoxygenase enzymes. So the presence of DGLA and EPA in tissues lowers the output of AA's eicosanoids.
Counteraction—Some DGLA and EPA derived eicosanoids counteract their AA derived counterparts.

Role in inflammation

Since antiquity

Aulus Cornelius Celsus

Aulus Cornelius Celsus was a Roman encyclopedist, known for his extant medical work, De Medicina, which is believed to be the only surviving section of a much larger encyclopedia. The De Medicina is a primary source on diet, pharmacy, surgery and related fields, and it is one of the best sources...

, the cardinal signs of inflammation have been known as: calor (warmth), dolor (pain), tumor (swelling) and rubor (redness). The eicosanoids are involved with each of these signs.

Redness

Erythema

Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...

—An insect's sting will trigger the classic inflammatory response. Short acting vasoconstrictors — TXA₂—are released quickly after the injury. The site may momentarily turn pale. Then TXA₂ mediates the release of the vasodilators PGE₂ and LTB₄. The blood vessels engorge and the injury reddens.

Swelling

Edema

Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

—LTB₄ makes the blood vessels more permeable. Plasma leaks out into the connective tissues, and they swell. The process also loses pro-inflammatory cytokines.

Pain

Hyperalgesia

Hyperalgesia is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.-Types:...

—The cytokines increase COX-2 activity. This elevates levels of PGE₂, sensitizing pain neurons.

Heat

Fever

Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

—PGE₂ is also a potent pyretic agent. Aspirin and NSAIDS—drugs that block the COX pathways and stop prostanoid synthesis—limit fever or the heat of localized inflammation.

Pharmacy: Eicosanoid, eicosanoid analogs and receptor agonists/antagonists used as medicines
Medicine	Type	Medical condition or use
Alprostadil Alprostadil Prostaglandin E1 , known pharmaceutically as alprostadil, is a prostaglandin. It is a drug used in the treatment of erectile dysfunction and has vasodilatory properties.-Sexual dysfunction:...	PGE₁	Erectile dysfunction Erectile dysfunction Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance.... , maintaining a patent ductus arteriosus Patent ductus arteriosus Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain... in the fetus Fetus A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
Beraprost Beraprost Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the treatment of pulmonary hypertension. It is also being studied for use in avoiding reperfusion injury.-Clinical pharmacology:...	PGI₁ analog	Pulmonary hypertension Pulmonary hypertension In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion... , avoiding reperfusion injury Reperfusion injury Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and...
Bimatoprost Bimatoprost Bimatoprost is a prostaglandin analog/prodrug used topically to control the progression of glaucoma and in the management of ocular hypertension. It reduces intraocular pressure by increasing the outflow of aqueous fluid from the eyes...	PG analog	Glaucoma Glaucoma Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye... , ocular hypertension Hypertension Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
Carboprost Carboprost Carboprost is a synthetic prostaglandin analogue of PGF2α with oxytocic properties....	PG analog	Labor induction Induction (birth) Labor induction is a method of artificially or prematurely stimulating childbirth in a woman.-Indications:Common suggested reasons for induction include:* Postterm pregnancy, i.e. if the pregnancy has gone past the 42 week mark.... , abortifacient Abortifacient An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots.... in early pregnancy
Dinoprostone Dinoprostone The naturally occurring prostaglandin E2 is known in medicine as dinoprostone. It has important effects in labour and also stimulates osteoblasts to release factors that stimulate bone resorption by osteoclasts...	PGE₂	Labor induction Induction (birth) Labor induction is a method of artificially or prematurely stimulating childbirth in a woman.-Indications:Common suggested reasons for induction include:* Postterm pregnancy, i.e. if the pregnancy has gone past the 42 week mark....
Iloprost Iloprost Iloprost is a drug used to treat pulmonary arterial hypertension , scleroderma, Raynaud's phenomenon and ischemia. It was developed by the pharmaceutical company Schering AG and is marketed by Bayer Schering Pharma AG in Europe and Actelion Pharmaceuticals in the USA.-Clinical pharmacology:Iloprost...	PGI₂ analog	Pulmonary arterial hypertension Pulmonary hypertension In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
Latanoprost Latanoprost Latanoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension by reducing intraocular pressure...	PG analog	Glaucoma Glaucoma Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye... , ocular hypertension Hypertension Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
Misoprostol Misoprostol Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D...	PGE₁ analog	Stomach ulcers Peptic ulcer A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm... , labor induction Induction (birth) Labor induction is a method of artificially or prematurely stimulating childbirth in a woman.-Indications:Common suggested reasons for induction include:* Postterm pregnancy, i.e. if the pregnancy has gone past the 42 week mark.... , abortifacient Abortifacient An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....
Montelukast Montelukast Montelukast is a leukotriene receptor antagonist used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally...	LT receptor antagonist Receptor antagonist A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...	Asthma Asthma Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath... , seasonal allergies Allergy An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
Travoprost Travoprost Travoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension, by reducing intraocular pressure. It is a synthetic prostaglandin analog that works by increasing the outflow of aqueous fluid from the eyes...	PG analog	Glaucoma Glaucoma Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye... , ocular hypertension Hypertension Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
Treprostinil Treprostinil Treprostinil is a synthetic analog of prostacyclin .-History:...	PGI analog	Pulmonary hypertension Pulmonary hypertension In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
U46619 U46619 U46619 is a stable synthetic analog of the prostaglandin PGH2 first prepared in 1975. U46619 is a vasoconstrictor that mimics the hydroosmotic effect of vasopressin. It also mimics the effects of thromboxane by activating phospholipase C....	Longer lived TX analog	Research only
Zafirlukast Zafirlukast Zafirlukast is an oral leukotriene receptor antagonist for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast...	LT receptor antagonist Receptor antagonist A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...	Asthma Asthma Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

Action of prostanoids

Main articles: Prostaglandin

Prostaglandin

, Prostacyclin

Prostacyclin

Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...

and Thromboxane

Thromboxane

Prostanoids mediate local symptoms of inflammation

Inflammation

: vasoconstriction

Vasoconstriction

Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

or vasodilation

Vasodilation

Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...

, coagulation

Coagulation

Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...

, pain

Pain

Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

and fever

Fever

. Inhibition of cyclooxygenase

Cyclooxygenase

, specifically the inducible COX-2 isoform, is the hallmark of NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin

Aspirin

. COX-2 is responsible for pain and inflammation, while COX-1 is responsible for platelet clotting actions.

Prostanoids activate the PPAR_γ members of the steroid/thyroid family of nuclear hormone receptors

Nuclear receptor

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...

, directly influencing gene transcription

Transcription (genetics)

Action of leukotrienes

Leukotrienes play an important role in inflammation. There is a neuroendocrine role for LTC₄ in luteinizing hormone

Luteinizing hormone

Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

secretion. LTB₄ causes adhesion and chemotaxis

Chemotaxis

Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...

of leukocytes and stimulates aggregation, enzyme release, and generation of superoxide

Superoxide

A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...

in neutrophils. Blocking leukotriene receptors can play a role in the management of inflammatory diseases such as asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

(by the drugs montelukast

Montelukast

Montelukast is a leukotriene receptor antagonist used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally...

and zafirlukast

Zafirlukast

Zafirlukast is an oral leukotriene receptor antagonist for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast...

), psoriasis

Psoriasis

Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

, and rheumatoid arthritis

Rheumatoid arthritis

.

The slow reacting substance of anaphylaxis

Slow reacting substance of anaphylaxis

The Slow-reacting substance of anaphylaxis or SRS-A is a mixture of the leukotrienes LTC4, LTD4 and LTE4. Mast cells secrete it during the anaphylactic reaction, inducing inflammation. It can be found in basophils....

comprises the cysteinyl leukotrienes. These have a clear role in pathophysiological

Pathophysiology

Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...

conditions such as asthma, allergic rhinitis

Hay Fever

Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...

and other nasal allergies, and have been implicated in atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

and inflammatory gastrointestinal diseases

Digestive disease

All diseases that pertain to the gastrointestinal tract are labelled as digestive diseases. This includes diseases of the esophagus, stomach, first, second, and third part of the duodenum, jejunum, ileum, the ileo-cecal complex, large intestine , sigmoid colon, and rectum.-Esophagus:*Esophagitis -...

.
They are potent bronchoconstrictors, increase vascular permeability in postcapillary venule

Venule

A venule is a very small blood vessel in the microcirculation that allows deoxygenated blood to return from the capillary beds to the larger blood vessels called veins. Venules range from 8 to 100μm in diameter and are formed when capillaries unite .Venules are blood vessels that drain blood...

s, and stimulate mucus

Mucus

In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...

secretion. They are released from the lung tissue of asthmatic subjects exposed to specific allergens and play a pathophysiological role in immediate hypersensitivity

Allergy

An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...

reactions.
Along with PGD, they function in effector cell trafficking, antigen presentation, immune cell activation, matrix deposition

Osteocyte

An osteocyte, a star-shaped cell, is the most abundant cell found in compact bone. Cells contain a nucleus and a thin ring of cytoplasm. When osteoblasts become trapped in the matrix they secrete, they become osteocytes...

, and fibrosis

Fibrosis

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

History

In 1930, gynecologist Raphael Kurzrok and pharmacologist Charles Leib characterized prostaglandin

Prostaglandin

as a component of semen.
Between 1929 and 1932, Burr and Burr showed that restricting fat from animal's diets led to a deficiency disease, and first described the essential fatty acid

Essential fatty acid

Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them...

s.
In 1935, von Euler

Ulf von Euler

Ulf Svante von Euler was a Swedish physiologist and pharmacologist. He won a Nobel Prize in Physiology or Medicine in 1970 for his work on neurotransmitters.-Life:...

identified prostaglandin.
In 1964, Bergström

Sune Bergström

Karl Sune Detlof Bergström was a Swedish biochemist.In 1975, he was appointed to the Nobel Foundation Board of Directors in Sweden....

and Samuelsson

Bengt I. Samuelsson

-External links:**...

linked these observations when they showed that the "classical" eicosanoids were derived from arachidonic acid, which had earlier been considered to be one of the essential fatty acids.
In 1971, Vane

John Robert Vane

Sir John Robert Vane FRS was an English pharmacologist and Nobel Laureate, born in Tardebigg, Worcestershire. His father was the son of Russian immigrants and his mother came from a Worcestershire farming family. He was educated at King Edward's School in Edgbaston, Birmingham, and studied...

showed that aspirin and similar drugs inhibit prostaglandin synthesis. Von Euler received the Nobel Prize

Nobel Prize

The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

in medicine in 1970, which
Samuelsson, Vane, and Bergström also received in 1982.
E. J. Corey

Elias James Corey

Elias James Corey is an American organic chemist. In 1990 he won the Nobel Prize in Chemistry "for his development of the theory and methodology of organic synthesis", specifically retrosynthetic analysis...

received it in chemistry in 1990 largely for his synthesis of prostaglandins.

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