TRPV1
Encyclopedia
The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin
receptor and the vanilloid receptor 1, is a protein
that, in humans, is encoded by the TRPV1 gene
. It was the first isolated member of the transient receptor potential vanilloid receptor proteins which in turn are a sub family of the transient receptor potential protein group. This protein is a member of the TRPV
group of transient receptor potential family of ion channel
s.
The function of TRPV1 is detection and regulation of body temperature. Additionally, TRPV1 provides sensation of scalding heat and pain (nociception
).
and endogenous
physical and chemical stimuli. The best-known activators of TRPV1 are heat greater than 43°C, capsaicin
, the pungent compound in hot chili peppers, and allyl isothiocyanate
, the pungent compound in mustard and wasabi. The activation of TRPV1 leads to painful, burning sensation. Its endogenous activators include: low pH
(acidic conditions), the endocannabinoid anandamide
, N-arachidonoyl-dopamine
. TRPV1 receptors are found mainly in the nociceptive neurons of the peripheral nervous system
, but they have also been described in many other tissues, including the central nervous system
. TRPV1 is involved in the transmission and modulation of pain
(nociception
), as well as the integration of diverse painful stimuli.
, a number of inflammatory mediators, such as various prostaglandins and bradykinin
, are released. These agents increase the sensitivity of nociceptors to noxious stimuli. This manifests as an increased sensitivity to painful stimuli (hyperalgesia
) or pain sensation in response to non-painful stimuli allodynia
. Most sensitizing pro-inflammatory agents activate the phospholipase C
pathway. Phopshorylation of TRPV1 by protein kinase C
have been shown to play a role in sensitzation of TRPV1.
, TRPV1 activity decreases, a phenomenon called desensitization. Extracellular calcium
ions are required for this phenomenon, thus influx of calcium and the consequential increase of intracellular calcium mediate this effect. Various signaling pathways such as calmodulin
and calcineurin
, and the decrease of PIP2, have been implicated in desensitization of TRPV1. Desensitization of TRPV1 is thought to underlie the paradoxical analgesic
effect of capsaicin.
, TRPV1 has been a prime target for the development of novel pain reducers (analgesics). Two major strategies have been used:
block TRPV1 activity, thus reducing pain. These agents could be useful when applied systemically. Numerous TRPV1 antagonists have been developed by pharmaceutical companies. TRPV1 antagonists
have shown efficacy in reducing nociception
from inflammatory and neuropathic pain
models in rats. This provides evidence that TRPV1 is the capsaicin
's sole receptor.
In humans, drugs acting at TRPV1 receptors could be used to treat neuropathic pain associated with multiple sclerosis
, chemotherapy
, or amputation
, as well as pain associated with the inflammatory response of damaged tissue, such as in osteoarthritis
.
The major roadblock for the usefulness of these drugs is their effect on body temperature (hyperthermia
).
The role of TRPV1 in the regulation of body temperature has emerged in the last few years. Based on a number of TRPV-selective antagonist
s' causing an increase in body temperature (hyperthermia
), it was proposed that TRPV1 is tonically active in vivo and regulates body temperature by telling the body to "cool itself down". Without these signals, the body overheats. Similarly, this explains the propensity of capsaicin (a TRPV1 agonist) to cause sweating (i.e.: a signal to reduce body temperature). In a recent report, it was found that tonically active TRPV1 channels are present in the viscera and keep an ongoing suppressive effect on body temperature. Recently, it was proposed that predominant function of TRPV1 is body temperature maintenance Experiments have shown that TRPV1 blockade increases body temperature in multiple species, including rodents and humans, suggesting that TRPV1 is involved in body temperature maintenance. Recently, AMG 517, a highly selective TRPV1 antagonist was dropped out of clinical trials due to the undesirable level of hyperthermia. A second molecule, SB-705498 was also evaluated in the clinic but its effect on body temperature was not reported. Recently, it was disclosed that clinical trials of two more TRPV1 antagonists, GRC 6211 and NGD 8243 have been stopped. Post translational modification of TRPV1 protein by its phosphorylation
is critical for its functionality. Recent reports published from NIH suggest that Cdk5 mediated phosphorylation of TRPV1 is required for its ligand-induced channel opening.
and resiniferatoxin
activate TRPV1, and, upon prolonged application TRPV1 activity, would decrease (desensitization), leading to alleviation of pain. Agonists can be applied locally to the painful area as through a patch or an ointment. Numerous capsaicin-containing creams are available over the counter, containing low concentrations of capsaicin (0.025 - 0.075%). It is debated whether these preparations actually lead to TRPV1 desensitization, it is possible that they act via counter-irritation. Novel preparations containing higher capsaicin concentration (up to 10%) are under clinical trials. 8% capsaicin patches have recently become available for clinical use, with supporting evidence demonstrating that a 30 minute treatment can provide up to 3 months analgesia by causing regression of TRPV1 containing neurones in the skin.
and has been proposed as a target for treatment not only of pain but also for other conditions such as anxiety
.
Furthermore TRPV1 appears to mediate long term depression (LTD) in the hippocampus
. LTD has been linked to a decrease in the ability to make new memories, unlike its opposite long term potentiation (LTP), which aids in memory formation. A dynamic pattern of LTD and LTP occurring at many synapses provides a code for memory formation. Long-term depression and subsequent pruning of synapses with reduced activity is an important aspect of memory formation. In rat brain slices, activation of TRV1 with heat or capsaicin induced LTD while capsazepine blocked capsaicin's ability to induce LTD. In the brain stem (solitary tract nucleus), TRPV1 controls the asynchronous and spontaneous release of glutamate from unmyelinated cranial visceral afferents - release processes that are active at normal temperatures and hence quite distinct from TRPV1 responses in painful heat. Hence there may be therapeutic potential in modulating TRPV1 in the central nervous system, perhaps as a treatment for epilepsy (TRPV1 is already a target in the peripheral nervous system for pain relief).
of genes expressed in dorsal root ganglion
neurons, expressed the clones in HEK 293 cells and looked for cells which respond to capsaicin with calcium influx (which HEK-293 normally not do). After several rounds of screening and diving the library a single clone encoding the TRPV1 channel was finally identified in 1997. It was the first TRPV channel to be identified.
with Calmodulin 1
, SYT9
and SNAPAP
.
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...
receptor and the vanilloid receptor 1, is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the TRPV1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It was the first isolated member of the transient receptor potential vanilloid receptor proteins which in turn are a sub family of the transient receptor potential protein group. This protein is a member of the TRPV
TRPV
TRPV is a family of transient receptor potential ion channels. These channels are selective for calcium and magnesium over sodium ions. Like other members of the TRP superfamily, TRPV channels can be activated through seemingly disparate mechanisms...
group of transient receptor potential family of ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s.
The function of TRPV1 is detection and regulation of body temperature. Additionally, TRPV1 provides sensation of scalding heat and pain (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...
).
Function
TRPV1 is a nonselective cation channel that may be activated by a wide variety of exogenousExogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
and 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...
physical and chemical stimuli. The best-known activators of TRPV1 are heat greater than 43°C, 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...
, the pungent compound in hot chili peppers, and allyl isothiocyanate
Allyl isothiocyanate
Allyl isothiocyanate is the organosulfur compound with the formula CH2CHCH2NCS. This colorless oil is responsible for the pungent taste of mustard, horseradish, and wasabi. This pungency and the lachrymatory effect of AITC is mediated through the TRPA1 and TRPV1 ion channels...
, the pungent compound in mustard and wasabi. The activation of TRPV1 leads to painful, burning sensation. Its endogenous activators include: low pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
(acidic conditions), the endocannabinoid 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...
, N-arachidonoyl-dopamine
N-arachidonoyl-dopamine
N-Arachidonoyl dopamine is an endocannabinoid which acts as an agonist of the CB1 receptor and the transient receptor potential V1 ion channel. Its discovery was described in 2002 by an academic research group from Italy and the USA. It was found in the brain of rats, with especially high...
. TRPV1 receptors are found mainly in the nociceptive neurons of the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
, but they have also been described in many other tissues, including 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...
. TRPV1 is involved in the transmission and modulation 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."...
(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...
), as well as the integration of diverse painful stimuli.
Sensitization
The sensitivity of TRPV1 to noxious stimuli, such as high temperatures is not static. Upon tissue damage and the consequent inflammationInflammation
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...
, a number of inflammatory mediators, such as various prostaglandins and bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
, are released. These agents increase the sensitivity of nociceptors to noxious stimuli. This manifests as an increased sensitivity to painful stimuli (hyperalgesia
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:...
) or pain sensation in response to non-painful stimuli allodynia
Allodynia
Allodynia is a pain due to a stimulus which does not normally provoke pain. Temperature or physical stimuli can provoke allodynia, and it often occurs after injury to a site...
. Most sensitizing pro-inflammatory agents activate the 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...
pathway. Phopshorylation of TRPV1 by protein kinase 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...
have been shown to play a role in sensitzation of TRPV1.
Desensitization
Upon prolonged exposure to capsaicinCapsaicin
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...
, TRPV1 activity decreases, a phenomenon called desensitization. Extracellular calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ions are required for this phenomenon, thus influx of calcium and the consequential increase of intracellular calcium mediate this effect. Various signaling pathways such as calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...
and calcineurin
Calcineurin
Calcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
, and the decrease of PIP2, have been implicated in desensitization of TRPV1. Desensitization of TRPV1 is thought to underlie the paradoxical analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
effect of capsaicin.
Peripheral nervous system
Treatment of pain is an unmet medical need costing billions of dollars every year. As a result of its involvement 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...
, TRPV1 has been a prime target for the development of novel pain reducers (analgesics). Two major strategies have been used:
Antagonists
AntagonistsReceptor 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...
block TRPV1 activity, thus reducing pain. These agents could be useful when applied systemically. Numerous TRPV1 antagonists have been developed by pharmaceutical companies. TRPV1 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...
have shown efficacy in reducing 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...
from inflammatory and neuropathic pain
Neuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
models in rats. This provides evidence that TRPV1 is the 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...
's sole receptor.
In humans, drugs acting at TRPV1 receptors could be used to treat neuropathic pain associated with multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, or amputation
Amputation
Amputation is the removal of a body extremity by trauma, prolonged constriction, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on individuals as a preventative surgery for...
, as well as pain associated with the inflammatory response of damaged tissue, such as in osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
.
The major roadblock for the usefulness of these drugs is their effect on body temperature (hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
).
The role of TRPV1 in the regulation of body temperature has emerged in the last few years. Based on a number of TRPV-selective 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' causing an increase in body temperature (hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
), it was proposed that TRPV1 is tonically active in vivo and regulates body temperature by telling the body to "cool itself down". Without these signals, the body overheats. Similarly, this explains the propensity of capsaicin (a TRPV1 agonist) to cause sweating (i.e.: a signal to reduce body temperature). In a recent report, it was found that tonically active TRPV1 channels are present in the viscera and keep an ongoing suppressive effect on body temperature. Recently, it was proposed that predominant function of TRPV1 is body temperature maintenance Experiments have shown that TRPV1 blockade increases body temperature in multiple species, including rodents and humans, suggesting that TRPV1 is involved in body temperature maintenance. Recently, AMG 517, a highly selective TRPV1 antagonist was dropped out of clinical trials due to the undesirable level of hyperthermia. A second molecule, SB-705498 was also evaluated in the clinic but its effect on body temperature was not reported. Recently, it was disclosed that clinical trials of two more TRPV1 antagonists, GRC 6211 and NGD 8243 have been stopped. Post translational modification of TRPV1 protein by its phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
is critical for its functionality. Recent reports published from NIH suggest that Cdk5 mediated phosphorylation of TRPV1 is required for its ligand-induced channel opening.
Agonists
Agonists such as capsaicinCapsaicin
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...
and resiniferatoxin
Resiniferatoxin
Resiniferatoxin is a naturally occurring, ultrapotent capsaicin analog that activates the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception...
activate TRPV1, and, upon prolonged application TRPV1 activity, would decrease (desensitization), leading to alleviation of pain. Agonists can be applied locally to the painful area as through a patch or an ointment. Numerous capsaicin-containing creams are available over the counter, containing low concentrations of capsaicin (0.025 - 0.075%). It is debated whether these preparations actually lead to TRPV1 desensitization, it is possible that they act via counter-irritation. Novel preparations containing higher capsaicin concentration (up to 10%) are under clinical trials. 8% capsaicin patches have recently become available for clinical use, with supporting evidence demonstrating that a 30 minute treatment can provide up to 3 months analgesia by causing regression of TRPV1 containing neurones in the skin.
Central nervous system
TRPV1 is also expressed at high levels in 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...
and has been proposed as a target for treatment not only of pain but also for other conditions such as 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,...
.
Furthermore TRPV1 appears to mediate long term depression (LTD) in the 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...
. LTD has been linked to a decrease in the ability to make new memories, unlike its opposite long term potentiation (LTP), which aids in memory formation. A dynamic pattern of LTD and LTP occurring at many synapses provides a code for memory formation. Long-term depression and subsequent pruning of synapses with reduced activity is an important aspect of memory formation. In rat brain slices, activation of TRV1 with heat or capsaicin induced LTD while capsazepine blocked capsaicin's ability to induce LTD. In the brain stem (solitary tract nucleus), TRPV1 controls the asynchronous and spontaneous release of glutamate from unmyelinated cranial visceral afferents - release processes that are active at normal temperatures and hence quite distinct from TRPV1 responses in painful heat. Hence there may be therapeutic potential in modulating TRPV1 in the central nervous system, perhaps as a treatment for epilepsy (TRPV1 is already a target in the peripheral nervous system for pain relief).
Discovery
The DRG neurons of mammals were known to express a heat-sensitive ion channel which could be activated by capsaicin. The research group of David Julius therefore created a cDNA libraryCDNA library
A cDNA library is a combination of cloned cDNA fragments inserted into a collection of host cells, which together constitute some portion of the transcriptome of the organism. cDNA is produced from fully transcribed mRNA found in the nucleus and therefore contains only the expressed genes of an...
of genes expressed in dorsal root ganglion
Dorsal root ganglion
In anatomy and neuroscience, a dorsal root ganglion is a nodule on a dorsal root that contains cell bodies of neurons in afferent spinal nerves.-Unique unipolar structure:...
neurons, expressed the clones in HEK 293 cells and looked for cells which respond to capsaicin with calcium influx (which HEK-293 normally not do). After several rounds of screening and diving the library a single clone encoding the TRPV1 channel was finally identified in 1997. It was the first TRPV channel to be identified.
Interactions
TRPV1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Calmodulin 1
Calmodulin 1
Calmodulin 1 is a protein that in humans is encoded by the CALM1 gene.- Function :Calmodulin 1 is the archetype of the family of calcium-modulated proteins of which nearly 20 members have been found. They are identified by their occurrence in the cytosol or on membranes facing the cytosol and by a...
, SYT9
SYT9
Synaptotagmin-9 is a protein that in humans is encoded by the SYT9 gene.-Interactions:SYT9 has been shown to interact with SYNCRIP, TUBB and TRPV1.-Further reading:...
and SNAPAP
SNAPAP
SNARE-associated protein Snapin is a protein that in humans is encoded by the SNAPIN gene.-Interactions:SNAPAP has been shown to interact with SNAP-25, BLOC1S1, SNAP23, Dysbindin, TRPV1, PLDN, BLOC1S2 and RGS7.-Further reading:...
.
Hacking
One example of modularity and hacking opportunity is the heat activation domain. TRPV proteins are activated by heat on the C-termimus, while TRPM proteins are activated by cold temperatures (<23-28°C) in the same location. Exchanging the C-terminals for each other, could then activate these proteins at different than normal temperatures. Chemical genetics has also been used to introduce TRPV1 into cells that do not normally express it. When capsaicin is added, those cells are then activated by the influx of calcium. This system is not as fast as other controls, such as optogenetics, but remains an important mechanism of spatial and temporal control. This method of control can be applied to a variety of systems and cells, and will most likely be expanded and improved in the near future.See also
- CapsaicinCapsaicinCapsaicin 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...
- CapsinoidsCapsinoidsCapsinoids, which include capsiate, dihydrocapsiate, and nordihydrocapsiate, are substances naturally present in chili peppers. Although they are structurally similar to capsaicin, the substance that causes pungency in hot peppers, they largely lack that characteristic. Capsinoids have an...
- Vanilloid
- Cannabinoid receptorCannabinoid receptorThe 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...
- Discovery and development of TRPV1 antagonistsDiscovery and development of TRPV1 antagonistsChronic pain remains a recognized unmet medical need. Consequently, the search for new analgesic agents is being intensively studied by the pharmaceutical industry. The TRPV1 receptor is an ion channel that has been implicated in mediation of many types of pain and therefore studied most extensively...