Cannabinoid receptor type 1
Encyclopedia
The cannabinoid receptor type 1, often abbreviated to CB1, is a G protein-coupled
cannabinoid receptor
located in the brain
. It is activated by endocannabinoid neurotransmitter
s including anandamide
and by the compound THC
, found in the psychoactive drug
cannabis
.
G protein-coupled receptors in the brain. This is key to endocannabinoid-mediated depolarization-induced suppression of inhibition
, a very common form of short-term plasticity
in which the depolarization of a single neuron induces a reduction in GABA
-mediated neurotransmission. Endocannabinoids released from the depolarized neuron bind to CB1 receptors in the pre-synaptic neuron and cause a reduction in GABA release. Varying levels of CB1 expression can be detected in the olfactory bulb
, cortical
regions (neocortex
, pyriform cortex
, hippocampus
, and amygdala
), several parts of basal ganglia
, thalamic
and hypothalamic
nuclei and other subcortical regions (e.g. the septal region
), cerebellar cortex, and brainstem nuclei (e.g. the periaqueductal gray
).
, in the thyroid gland, and most likely in the adrenal gland
. CB1 is also expressed in several cells relating to metabolism, such as fat cells
, muscle cells, liver cells
(and also in the endothelial cells
, Kupffer cell
s and stellate cells
of the liver
), and in the digestive tract
. It is also expressed in the lungs and the kidney
.
CB1 is present on Leydig cells and human sperms
. In females, it is present in the ovaries, oviduct
s myometrium
, decidua
and placenta
. It is probably important also for the embryo
.
MK-9470
makes it possible to produce in vivo images of the distribution of CB1 receptors in the human brain with positron emission tomography
.
, Activation of presynaptic CB1 receptors is also known to inhibit sympathetic innervation of blood vessels and contributes to the suppression of the neurogenic vasopressor response in septic shock
.
activity has been observed after administration of Δ9-THC, or of anandamide
. This effect has been assumed to be CB1-mediated since the specific CB1 antagonist SR 141716A (Rimonabant
) blocks the effect. Another report, however, suggests that inhibition of intestinal
motility
may also have a CB2
-mediated component.
activity. Activation of peripheral CB1 receptors contributes to hemorrhagic
and endotoxin
-induced hypotension
. Anandamide and 2-AG, produced by macrophages and platelet
s respectively, may mediate this effect.
-induced chemical damage. This effect is produced by interaction with CB1 (or CB1-like) receptors, located on peripheral endings of sensory neuron
s involved in pain transmission. Palmitoylethanolamide
, which like anandamide is present in the skin
, also exhibits peripheral antinociceptive activity during the late phase of pain behavior. Palmitoylethanolamide, however, does not bind to either CB1 or CB2. Its analgesic activity is blocked by the specific CB2 antagonist SR144528, though not by the specific CB1 antagonist SR141716A
. Hence a CB2-like receptor was postulated.
(see Rimonabant
). A substantial number of antagonists of the CB1 receptor have been discovered and characterized. TM38837
has been developed as a CB1 receptor antagonist that is restricted to targeting only peripheral CB1 receptors.
, generated naturally inside the body (endocannabinoids) or introduced into the body as cannabis
or a related synthetic
compound. They are activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner.
After the receptor is engaged, multiple intracellular
signal transduction
pathways are activated. At first, it was thought that cannabinoid receptors mainly activated the G protein
Gi
, which inhibits the enzyme
adenylate cyclase
(and thereby the production of the second messenger molecule cyclic AMP), and positively influenced inwardly rectifying potassium channels
(=Kir or IRK). However, a much more complex picture has appeared in different cell types, implicating other potassium ion channels, calcium channel
s, protein kinase A and C
, Raf-1
, ERK
, JNK, p38
, c-fos
, c-jun
and many more.
Elimination of clinically undesirable psychotropic effects has not been reported with agonists that bind to cannabinoid receptors. THC, as well as the two major endogenous
compounds identified so far that bind to the cannabinoid receptors (anandamide
and 2-arachidonylglycerol) produce most of their effects by binding to both the CB1 and CB2 cannabinoid receptors.
The CB1 receptor can also be modulated allosterically synthetic ligands. in a positive and negative manner. In vivo
exposure to Δ9THC impairs long-term potentiation
and leads to a reduction of phosphorilated CREB
.
phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of mammals, and contributed to reveal that placental orders are distributed into four major clades: Xenarthra
, Afrotheria
, Laurasiatheria
, and Euarchonta
plus Glires
. CNR1 has also proven useful at lower taxonomic levels, e.g., in rodents, and for the identification of dermopterans as the closest primate relatives.
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...
cannabinoid receptor
Cannabinoid receptor
The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains...
located in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. It is activated by endocannabinoid neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s including anandamide
Anandamide
Anandamide, also known as N-arachidonoylethanolamide or AEA, is an endogenous cannabinoid neurotransmitter. The name is taken from the Sanskrit word ananda, which means "bliss, delight", and amide. It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways...
and by the compound THC
Tetrahydrocannabinol
Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...
, found in the psychoactive drug
Psychoactive drug
A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...
cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
.
Expression
The CB1 receptor is encoded by the gene or CNR1. Two transcript variants encoding different isoforms have been described for this gene. CNR1 orthologs have been identified in most mammals.Brain
CB1 receptors are thought to be the most widely expressedGene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
G protein-coupled receptors in the brain. This is key to endocannabinoid-mediated depolarization-induced suppression of inhibition
Depolarization-induced suppression of inhibition
Depolarization-induced suppression of inhibition is the classical and original electrophysiological example of endocannabinoid function in the central nervous system...
, a very common form of short-term plasticity
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...
in which the depolarization of a single neuron induces a reduction in GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
-mediated neurotransmission. Endocannabinoids released from the depolarized neuron bind to CB1 receptors in the pre-synaptic neuron and cause a reduction in GABA release. Varying levels of CB1 expression can be detected in the olfactory bulb
Olfactory bulb
The olfactory bulb is a structure of the vertebrate forebrain involved in olfaction, the perception of odors.-Anatomy:In most vertebrates, the olfactory bulb is the most rostral part of the brain. In humans, however, the olfactory bulb is on the inferior side of the brain...
, cortical
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
regions (neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
, pyriform cortex
Piriform cortex
In anatomy of animals, the piriform cortex, or pyriform cortex is a region in the brain.-Anatomy and function:The piriform cortex is part of the rhinencephalon situated in the telencephalon....
, hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, and amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
), several parts of basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, thalamic
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and hypothalamic
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
nuclei and other subcortical regions (e.g. the septal region
Septal nuclei
The septal area are structures that lie below the rostrum of corpus callosum in front of lamina terminalis , composed of medium-size neurons grouped into medial, lateral, and posterior groups...
), cerebellar cortex, and brainstem nuclei (e.g. the periaqueductal gray
Periaqueductal gray
Periaqueductal gray is the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain. It plays a role in the descending modulation of pain and in defensive behaviour...
).
Other
CB1 is expressed on several cell types of the pituitary glandPituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, in the thyroid gland, and most likely in the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
. CB1 is also expressed in several cells relating to metabolism, such as fat cells
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...
, muscle cells, liver cells
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
(and also in the endothelial cells
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
, Kupffer cell
Kupffer cell
Kupffer cells, also known as Browicz-Kupffer cells and stellate macrophages, are specialized macrophages located in the liver lining the walls of the sinusoids that form part of the reticuloendothelial system .-History:The cells were first observed by Karl Wilhelm von Kupffer in 1876...
s and stellate cells
Hepatic stellate cell
Hepatic stellate cells , also known as perisinusoidal cells or Ito cells , are pericytes found in the perisinusoidal space of the liver also known as the space of Disse...
of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
), and in the digestive tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
. It is also expressed in the lungs and the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
.
CB1 is present on Leydig cells and human sperms
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...
. In females, it is present in the ovaries, oviduct
Oviduct
In non-mammalian vertebrates, the passageway from the ovaries to the outside of the body is known as the oviduct. The eggs travel along the oviduct. These eggs will either be fertilized by sperm to become a zygote, or will degenerate in the body...
s myometrium
Myometrium
The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells , but also of supporting stromal and vascular tissue...
, decidua
Decidua
Decidua is the term for the uterine lining during a pregnancy, which forms the maternal part of the placenta. It is formed under the influence of progesterone and forms highly-characteristic cells.-Etymology:...
and placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
. It is probably important also for the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
.
Neuroimaging
The inverse agonistInverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
MK-9470
MK-9470
MK-9470 is a synthetic compound, which binds to the CB1 cannabinoid receptor and functions as an inverse agonist....
makes it possible to produce in vivo images of the distribution of CB1 receptors in the human brain with positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
.
Liver
In the liver, activation of the CB1 receptor is known to increase de novo lipogenesisLipogenesis
Lipogenesis is the process by which acetyl-CoA is converted to fats. The former is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis, the energy can be efficiently stored in the form of fats...
, Activation of presynaptic CB1 receptors is also known to inhibit sympathetic innervation of blood vessels and contributes to the suppression of the neurogenic vasopressor response in septic shock
Septic shock
Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
.
Gastrointestinal activity
Inhibition of gastrointestinalGastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
activity has been observed after administration of Δ9-THC, or of anandamide
Anandamide
Anandamide, also known as N-arachidonoylethanolamide or AEA, is an endogenous cannabinoid neurotransmitter. The name is taken from the Sanskrit word ananda, which means "bliss, delight", and amide. It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways...
. This effect has been assumed to be CB1-mediated since the specific CB1 antagonist SR 141716A (Rimonabant
Rimonabant
Rimonabant is an anorectic antiobesity drug that has been withdrawn from the market. It is an inverse agonist for the cannabinoid receptor CB1...
) blocks the effect. Another report, however, suggests that inhibition of intestinal
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
motility
Motility
Motility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
may also have a CB2
Cannabinoid receptor 2 (macrophage)
Cannabinoid receptor 2 , also known as CB2 or CNR2, is a G protein-coupled receptor from the cannabinoid receptor family, which in humans is encoded by the CNR2 gene...
-mediated component.
Cardiovascular activity
Cannabinoids are well known for their cardiovascularCirculatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
activity. Activation of peripheral CB1 receptors contributes to hemorrhagic
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
and endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...
-induced hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
. Anandamide and 2-AG, produced by macrophages and platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s respectively, may mediate this effect.
Pain
Anandamide attenuates the early phase or the late phase of pain behavior produced by formalinFormaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
-induced chemical damage. This effect is produced by interaction with CB1 (or CB1-like) receptors, located on peripheral endings of sensory neuron
Sensory neuron
Sensory neurons are typically classified as the neurons responsible for converting external stimuli from the environment into internal stimuli. They are activated by sensory input , and send projections into the central nervous system that convey sensory information to the brain or spinal cord...
s involved in pain transmission. Palmitoylethanolamide
Palmitoylethanolamide
Palmitoylethanolamide is an endogenous fatty acid amide, belonging to the class of endocannabinoids. PEA has been demonstrated to bind to a receptor in the cell-nucleus and exerts a great variety of biological functions related to chronic pain and inflammation. The main target is thought to be...
, which like anandamide is present in the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, also exhibits peripheral antinociceptive activity during the late phase of pain behavior. Palmitoylethanolamide, however, does not bind to either CB1 or CB2. Its analgesic activity is blocked by the specific CB2 antagonist SR144528, though not by the specific CB1 antagonist SR141716A
Rimonabant
Rimonabant is an anorectic antiobesity drug that has been withdrawn from the market. It is an inverse agonist for the cannabinoid receptor CB1...
. Hence a CB2-like receptor was postulated.
Use of antagonists
CB1 selective antagonists are used for weight reduction and smoking cessationSmoking cessation
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
(see Rimonabant
Rimonabant
Rimonabant is an anorectic antiobesity drug that has been withdrawn from the market. It is an inverse agonist for the cannabinoid receptor CB1...
). A substantial number of antagonists of the CB1 receptor have been discovered and characterized. TM38837
TM38837
TM38837 is a new small molecule inverse inhibitor of the CB1 receptor Cannabinoid receptor. It is being developed for the treatment of obesity and metabolic disorders by 7TM Pharma...
has been developed as a CB1 receptor antagonist that is restricted to targeting only peripheral CB1 receptors.
Mechanism
Cannabinoid receptors are activated by cannabinoidsCannabinoids
Cannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
, generated naturally inside the body (endocannabinoids) or introduced into the body as cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
or a related synthetic
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
compound. They are activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner.
After the receptor is engaged, multiple intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
pathways are activated. At first, it was thought that cannabinoid receptors mainly activated the G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
Gi
Gi alpha subunit
Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors...
, which inhibits the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
adenylate cyclase
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....
(and thereby the production of the second messenger molecule cyclic AMP), and positively influenced inwardly rectifying potassium channels
Inward-rectifier potassium ion channel
Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
(=Kir or IRK). However, a much more complex picture has appeared in different cell types, implicating other potassium ion channels, calcium channel
Calcium channel
A Calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.-Comparison tables:...
s, protein kinase A and C
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
, Raf-1
C-Raf
RAF proto-oncogene serine/threonine-protein kinase also known as proto-oncogene c-RAF or simply c-Raf is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade...
, ERK
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
, JNK, p38
P38
P38 or P-38 may refer to:* Lockheed P-38 Lightning, a World War II American fighter aircraft built by Lockheed* p38 mitogen-activated protein kinases, a class of mitogen-activated protein kinases, two British Royal Navy ships...
, c-fos
C-Fos
In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...
, c-jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
and many more.
Elimination of clinically undesirable psychotropic effects has not been reported with agonists that bind to cannabinoid receptors. THC, as well as the two major endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
compounds identified so far that bind to the cannabinoid receptors (anandamide
Anandamide
Anandamide, also known as N-arachidonoylethanolamide or AEA, is an endogenous cannabinoid neurotransmitter. The name is taken from the Sanskrit word ananda, which means "bliss, delight", and amide. It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways...
and 2-arachidonylglycerol) produce most of their effects by binding to both the CB1 and CB2 cannabinoid receptors.
The CB1 receptor can also be modulated allosterically synthetic ligands. in a positive and negative manner. In vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
exposure to Δ9THC impairs long-term potentiation
Long-term potentiation
In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
and leads to a reduction of phosphorilated CREB
CREB
CREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....
.
Evolution
The CNR1 gene is used in animals as a nuclear DNANuclear DNA
Nuclear DNA, nuclear deoxyribonucleic acid , is DNA contained within a nucleus of eukaryotic organisms. In mammals and vertebrates, nuclear DNA encodes more of the genome than the mitochondrial DNA and is composed of information inherited from two parents, one male, and one female, rather than...
phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of mammals, and contributed to reveal that placental orders are distributed into four major clades: Xenarthra
Xenarthra
The superorder Xenarthra is a group of placental mammals , existent today only in the Americas and represented by anteaters, tree sloths, and armadillos. The origins of the order can be traced back as far as the Paleogene in South America...
, Afrotheria
Afrotheria
Afrotheria is a clade of mammals, the living members of which belong to groups from Africa or of African origin: golden moles, sengis , tenrecs, aardvarks, hyraxes, elephants and sea cows. The common ancestry of these animals was not recognized until the late 1990s...
, Laurasiatheria
Laurasiatheria
Laurasiatheria is a large group of placental mammals believed to have originated on the northern supercontinent of Laurasia. It includes shrews, hedgehogs, pangolins, bats, whales, most hoofed mammals, and carnivorans, among others....
, and Euarchonta
Euarchonta
The Euarchonta are a grandorder of mammals containing four orders: the Dermoptera or colugos, the Scandentia or treeshrews, the extinct Plesiadapiformes, and the Primates....
plus Glires
Glires
Glires is a clade consisting of rodents and lagomorphs . This hypothesis that these form a monophyletic group has been long debated based on morphological evidence, although recent morphological studies strongly support monophyly of Glires...
. CNR1 has also proven useful at lower taxonomic levels, e.g., in rodents, and for the identification of dermopterans as the closest primate relatives.