Substance P
Encyclopedia
In the field of neuroscience
, substance P (SP) is a neuropeptide
: an undecapeptide that functions as a neurotransmitter
and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A
(NKA) are produced from a polyprotein precursor after differential splicing of the preprotachykinin A gene. The deduced amino acid sequence of substance P is as follows:
Substance P is released from the terminals of specific sensory nerves, it is found in the brain and spinal cord, and is associated with inflammatory processes and pain
.
and John H. Gaddum as a tissue extract that caused intestinal contraction in vitro. Its tissue distribution and biologic actions were further investigated over the following decades. In 1983, NKA (previously known as substance K or neuromedin L) was isolated from porcine
spinal cord
and was also found to stimulate intestinal contraction.
receptor
for substance P is neurokinin 1
receptor (NK1-receptor, NK1R). It belongs to the tachykinin receptor
sub-family of GPCR
s. Other neurokinin subtypes and neurokinin receptors that interact with SP have also been reported. Amino acid residues that are responsible for the binding of SP and its antagonists
are present in the extracellular loops and transmembrane regions of NK-1. Binding of SP to NK-1 results in internalization by the clathrin
-dependent mechanism to the acidified endosome
s where the complex disassociates. SP is subsequently degraded and NK-1 is re-expressed on the cell surface. Substance P and the NK1 receptor are widely distributed in the brain and are specifically found in brain regions that regulate emotion (hypothalamus
, amygdala
, and the periaqueductal gray
). They are also found in close association with serotonin
(5-HT) and neurons containing norepinephrine that are targeted by the currently used antidepressant drugs. The SP receptor promoter contains regions that are sensitive to cAMP
, AP-1
, AP-4
, CEBPB
and epidermal growth factor
. Because these regions are related to complexed signal transduction pathways mediated by cytokines, it has been proposed that cytokines and neurotropic factors can induce NK-1. SP can also induce the cytokines that are capable of inducing NK-1 transcription factors.
. Substance P coexists with the excitatory neurotransmitter glutamate in primary afferents that respond to painful stimulation. Substance P has been associated with the regulation of mood disorders, anxiety
, stress
, reinforcement
, neurogenesis
, respiratory rhythm, neurotoxicity
, nausea
/emesis, pain
and nociception
. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle and joints. It is proposed that this release is involved in neurogenic inflammation
, which is a local inflammatory response to certain types of infection or injury. The regulatory function of SP also involves the regulation of its high-affinity receptor, NK-1. Substance P receptor antagonists may have important therapeutic applications in the treatment of a variety of stress-related illnesses, in addition to their potential as analgesics.
center in the medulla
contains high concentrations of substance P and its receptor, in addition to other neurotransmitters such as choline
, histamine
, dopamine
, serotonin
, and opioid
s. Their activation stimulates the vomiting reflex. Different emetic pathways exist, and substance P/NK1R appears to be within the final common pathway to regulate vomiting. Substance P antagonist (SPA) aprepitant
is available in the market in the treatment of chemotherapy
-induced nausea/emesis.
, transmitting information about tissue damage from peripheral receptors to the central nervous system
to be converted to the sensation of pain
. It has been theorized that it plays a part in fibromyalgia
. Capsaicin
has been shown to reduce the levels of substance P, it is presumed, by reducing the number of C-fibre nerves or causing these nerves to be more tolerant. Thus, Capsaicin is clinically used as an analgesic and an inflammatory agent to reduce pain associated with arthritis and many types of neuralgia. A role of substance P and NKA in nociception is suggested by the reduction in response thresholds to noxious stimuli by central administration of K2 and K3 agonists. Based on recent studies, it was proposed that NK1, and possibly the NK2 receptor antagonist
s, could be developed as analgesic drugs.
It has been studied that the mice carrying a disruption of the gene encoding SP/NKA show severely reduced nociceptive pain responses when the stimuli are moderate to intense. Pain behaviors induced by mechanical, thermal, and chemical stimulation of somatic and visceral tissues were reduced in the mutant mice lacking SP/NKA. However, it has been proposed that the importance of SP and NKA in animal's pain response apply only to a certain 'window' of pain intensities, and, when the intensity of the pain stimuli is further increased, the responses of the knockout mice
is not severely different from the wild-type mice.
Substance P increases glutamate activity (NMDA) in central nervous system, and it is associated with the development of brain edema and functional deficits after traumatic brain injury.
release. Substance P is involved in the axon reflex-mediated vasodilatation to local heating and wheal
and flare reaction. It has been shown that vasodilatation to substance P is dependent on the NK1 receptor located on the endothelium. In contrast to other neuropeptides studied in human skin, substance P-induced vasodilatation has been found to decline during continuous infusion. This possibly suggest an internalization of neurokinin-1 (NK1). As is typical with many vasodilators, it also has bronchoconstrictive
properties, administered through the non-adrenergic, non-cholinergic nervous system (branch of the vagal system).
.
is a single-celled parasitic protozoan that infects the lower gastrointestinal tract of humans. The symptoms of infection are diarrhea
, constipation
, and abdominal pain
. This protozoan was found to secrete serotonin
as well as substance P and neurotensin
.
s lack cutaneous C fibers reactive to substance P (SP) and many small neurons that are normally SP-positive. Thus, these animals are insensitive to pain
when painful stimuli are administered to the skin. New studies have shown that when the function of SP is genetically disrupted in mice, the animals demonstrated reduced responses to painful stimuli. Moreover, the response to capsaicin was absent or severely reduced in knockout mice
.
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
, substance P (SP) is a neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
: an undecapeptide that functions as a 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...
and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A
Neurokinin A
Neurokinin A is a member of the tachykinin family of neuropeptide neurotransmitters. It is produced from the same preprotachykinin A gene as the neuropeptide substance P. It has various roles in the body of humans and other animals...
(NKA) are produced from a polyprotein precursor after differential splicing of the preprotachykinin A gene. The deduced amino acid sequence of substance P is as follows:
- ArgArginineArginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
ProProlineProline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
LysLysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
ProProlineProline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
GlnGlutamineGlutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
GlnGlutamineGlutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
PhePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
PhePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
GlyGlycineGlycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
LeuLeucineLeucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
MetMethionineMethionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
Substance P is released from the terminals of specific sensory nerves, it is found in the brain and spinal cord, and is associated with inflammatory processes and 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."...
.
Discovery
Substance P was originally discovered in 1931 by Ulf von EulerUlf 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:...
and John H. Gaddum as a tissue extract that caused intestinal contraction in vitro. Its tissue distribution and biologic actions were further investigated over the following decades. In 1983, NKA (previously known as substance K or neuromedin L) was isolated from porcine
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
and was also found to stimulate intestinal contraction.
Receptor
The endogenousEndogenous
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...
receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
for substance P is neurokinin 1
Tachykinin receptor 1
The tachykinin receptor 1 also known as neurokinin 1 receptor or substance P receptor is a G protein coupled receptor found in the central nervous system and peripheral nervous system. The endogenous ligand for this receptor is Substance P, although it has some affinity for other tachykinins...
receptor (NK1-receptor, NK1R). It belongs to the tachykinin receptor
Tachykinin receptor
There are three known mammalian tachykinin receptors termed NK1, NK2 and NK3. All are members of the 7 transmembrane G-protein coupled receptor family and induce the activation of phospholipase C, producing inositol triphosphate ....
sub-family of GPCR
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...
s. Other neurokinin subtypes and neurokinin receptors that interact with SP have also been reported. Amino acid residues that are responsible for the binding of SP and its antagonists
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...
are present in the extracellular loops and transmembrane regions of NK-1. Binding of SP to NK-1 results in internalization by the clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
-dependent mechanism to the acidified endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
s where the complex disassociates. SP is subsequently degraded and NK-1 is re-expressed on the cell surface. Substance P and the NK1 receptor are widely distributed in the brain and are specifically found in brain regions that regulate emotion (hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, 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.-...
, and 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...
). They are also found in close association with serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(5-HT) and neurons containing norepinephrine that are targeted by the currently used antidepressant drugs. The SP receptor promoter contains regions that are sensitive to cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
, AP-1
AP-1 (transcription factor)
In the field of molecular biology, the activator protein 1 is a transcription factor which is a heterodimeric protein composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families. It regulates gene expression in response to a variety of stimuli, including cytokines, growth factors,...
, AP-4
TFAP4
Transcription factor AP-4 , also known as TFAP4, is a protein which in humans is encoded by the TFAP4 gene.- Function :...
, CEBPB
CEBPB
CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.- Function :The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins...
and epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
. Because these regions are related to complexed signal transduction pathways mediated by cytokines, it has been proposed that cytokines and neurotropic factors can induce NK-1. SP can also induce the cytokines that are capable of inducing NK-1 transcription factors.
Function
Substance P is an important element in pain perception. The sensory function of substance P is thought to be related to the transmission of pain information into the central nervous systemCentral 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...
. Substance P coexists with the excitatory neurotransmitter glutamate in primary afferents that respond to painful stimulation. Substance P has been associated with the regulation of mood disorders, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
, reinforcement
Reinforcement
Reinforcement is a term in operant conditioning and behavior analysis for the process of increasing the rate or probability of a behavior in the form of a "response" by the delivery or emergence of a stimulus Reinforcement is a term in operant conditioning and behavior analysis for the process of...
, neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
, respiratory rhythm, neurotoxicity
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
/emesis, 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 nociception
Nociception
Nociception is defined as "the neural processes of encoding and processing noxious stimuli." It is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue...
. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle and joints. It is proposed that this release is involved in neurogenic inflammation
Neurogenic inflammation
Neurogenic inflammation is inflammation arising from the local release from afferent neurons of inflammatory mediators such as Substance P and Calcitonin Gene-Related Peptide ....
, which is a local inflammatory response to certain types of infection or injury. The regulatory function of SP also involves the regulation of its high-affinity receptor, NK-1. Substance P receptor antagonists may have important therapeutic applications in the treatment of a variety of stress-related illnesses, in addition to their potential as analgesics.
Vomiting
The vomitingVomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
center in the medulla
Medulla
Medulla refers to the middle of something and derives from the Latin word for marrow. Its anatomical uses include:* Medulla oblongata, a part of the brain stem* Renal medulla, a part of the kidney* Adrenal medulla, a part of the adrenal gland...
contains high concentrations of substance P and its receptor, in addition to other neurotransmitters such as choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
, histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, and opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s. Their activation stimulates the vomiting reflex. Different emetic pathways exist, and substance P/NK1R appears to be within the final common pathway to regulate vomiting. Substance P antagonist (SPA) aprepitant
Aprepitant
Aprepitant is an antiemetic chemical compound that belongs to a class of drugs called substance P antagonists . It mediates its effect by blocking the neurokinin 1 receptor.Aprepitant is manufactured by Merck & Co...
is available in the market in the treatment of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
-induced nausea/emesis.
Pain
Substance P is involved in nociceptionNociception
Nociception is defined as "the neural processes of encoding and processing noxious stimuli." It is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue...
, transmitting information about tissue damage from peripheral receptors to 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...
to be converted to the sensation of 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."...
. It has been theorized that it plays a part in fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
. Capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
has been shown to reduce the levels of substance P, it is presumed, by reducing the number of C-fibre nerves or causing these nerves to be more tolerant. Thus, Capsaicin is clinically used as an analgesic and an inflammatory agent to reduce pain associated with arthritis and many types of neuralgia. A role of substance P and NKA in nociception is suggested by the reduction in response thresholds to noxious stimuli by central administration of K2 and K3 agonists. Based on recent studies, it was proposed that NK1, and possibly the NK2 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...
s, could be developed as analgesic drugs.
It has been studied that the mice carrying a disruption of the gene encoding SP/NKA show severely reduced nociceptive pain responses when the stimuli are moderate to intense. Pain behaviors induced by mechanical, thermal, and chemical stimulation of somatic and visceral tissues were reduced in the mutant mice lacking SP/NKA. However, it has been proposed that the importance of SP and NKA in animal's pain response apply only to a certain 'window' of pain intensities, and, when the intensity of the pain stimuli is further increased, the responses of the knockout mice
Knockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
is not severely different from the wild-type mice.
Substance P increases glutamate activity (NMDA) in central nervous system, and it is associated with the development of brain edema and functional deficits after traumatic brain injury.
Cell growth
Substance P has been known to stimulate cell growth in culture, and it was shown that substance P could promote wound healing of non-healing ulcers in humans.Diabetes
Substance P injected into pancreatic nerves has been shown to reverse diabetes in mice but effects to insulin secretion seems to be species dependent. In humans, substance P seems to decrease insulin release and cause fluctuations in blood sugar levels.Vasodilation
Substance P also has effects as a potent vasodilator. Substance P-induced vasodilatation is dependent on nitric oxideNitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
release. Substance P is involved in the axon reflex-mediated vasodilatation to local heating and wheal
Wheal
Wheal may refer to:*Wheal response, a cutaneous condition left by a blow or as part of an allergic reaction*Wheal, a Cornish mine...
and flare reaction. It has been shown that vasodilatation to substance P is dependent on the NK1 receptor located on the endothelium. In contrast to other neuropeptides studied in human skin, substance P-induced vasodilatation has been found to decline during continuous infusion. This possibly suggest an internalization of neurokinin-1 (NK1). As is typical with many vasodilators, it also has bronchoconstrictive
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....
properties, administered through the non-adrenergic, non-cholinergic nervous system (branch of the vagal system).
Eczema
High levels of BDNF and substance P have been found associated with increased itching in eczemaEczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
.
Gastrointestinal infection
Entamoeba histolyticaEntamoeba histolytica
Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide...
is a single-celled parasitic protozoan that infects the lower gastrointestinal tract of humans. The symptoms of infection are diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, and abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
. This protozoan was found to secrete serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
as well as substance P and neurotensin
Neurotensin
Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system...
.
Denervation supersensitivity
When the innervation to substance P nerve terminals is lost, post-synaptic cells compensate for the loss of adequate neurotransmitter by increasing the expression of post-synaptic receptors. This, ultimately, leads to a condition known as Denervation Supersensitivity as the post-synaptic nerves will become hypersensitive to any invasion of substance P into the synaptic cleft.Deficiency
Naked mole ratNaked Mole Rat
The naked mole rat , also known as the sand puppy or desert mole rat, is a burrowing rodent native to parts of East Africa and the only species currently classified in the genus Heterocephalus...
s lack cutaneous C fibers reactive to substance P (SP) and many small neurons that are normally SP-positive. Thus, these animals are insensitive to 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."...
when painful stimuli are administered to the skin. New studies have shown that when the function of SP is genetically disrupted in mice, the animals demonstrated reduced responses to painful stimuli. Moreover, the response to capsaicin was absent or severely reduced in knockout mice
Knockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
.