Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

encoding the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

of the same name. The TRPV3 protein belongs to a family of nonselective cation

channels Channel, channels, channeling, etc., may refer to: Geography * Channel (geography), in physical geography, a landform consisting of the outline (banks) of the path of a narrow body of water. Australia * Channel Country, region of outback Austral ...

that function in a variety of processes, including temperature sensation and vasoregulation. The thermosensitive members of this family are expressed in subsets of human

sensory neuron Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell ...

s that terminate in the skin, and are activated at distinct physiological temperatures. This channel is activated at temperatures between 22 and 40 degrees C. The gene lies in close proximity to another family member (

TRPV1 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 th ...

) gene on chromosome 17, and the two encoded proteins are thought to associate with each other to form heteromeric channels.

Function

The TRPV3 channel has wide tissue expression that is especially high in the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

(

keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...

s) but also in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

. It functions as a molecular sensor for innocuous warm temperatures. Mice lacking these protein are unable to sense elevated temperatures (>33 °C) but are able to sense cold and noxious heat. In addition to thermosensation TRPV3 channels seem to play a role in hair growth because mutations in the TRPV3 gene cause hair loss in mice. The role of TRPV3 channels in the brain is unclear, but appears to play a role in mood regulation. The protective effects of the natural product,

incensole acetate Insensole is an organic compound that is naturally found as its acetate ester in some frankincense. It is a diterpene alcohol, with an oily appearance. This compound can be synthetically prepared from cembrene. The formula of insensole is C20H3 ...

were partially mediated by TRPV3 channels.

Modulation

The TRPV3 channel is directly activated by various natural compounds like

carvacrol Carvacrol, or cymophenol, C6H3(CH3)(OH)C3H7, is a monoterpenoid phenol. It has a characteristic pungent, warm odor of oregano. Natural occurrence Carvacrol is present in the essential oil of ''Origanum vulgare'' (oregano), oil of thyme, oil ob ...

thymol Thymol (also known as 2-isopropyl-5-methylphenol, IPMP), , is a natural monoterpenoid phenol derivative of ''p''-Cymene, isomeric with carvacrol, found in oil of thyme, and extracted from ''Thymus vulgaris'' (common thyme), ajwain, and vario ...

and

eugenol Eugenol is an allyl chain-substituted guaiacol, a member of the allylbenzene class of chemical compounds. It is a colorless to pale yellow, aromatic oily liquid extracted from certain essential oils especially from clove, nutmeg, cinnamon, basil ...

. Several other

monoterpenoids Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen funct ...

which cause either feeling of warmth or are

skin sensitizer Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are ...

s can also open the channel. Monoterpenoids also induce agonist-specific desensitization of TRPV3 channels in a calcium-independent manner. Resolvin E1 (RvE1), RvD2, and 17''R''-RvD1 (see

resolvin Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. As autacoids similar ...

s) are metabolites of the

omega 3 fatty acid Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...

eicosapentaenoic acid Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-c ...

(for RvE1) or

docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-lino ...

(for RvD2 and 17''R''-RvD1). These metabolites are members of the

specialized proresolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...

(SPMs) class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, humans. These SPMs also dampen pain perception arising from various inflammation-based causes in animal models. The mechanism behind their pain-dampening effects involves the inhibition of TRPV3, probably (in at least certain cases) by an indirect effect wherein they activate other receptors located on neurons or nearby microglia or

astrocyte Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...

CMKLR1 Chemokine like receptor 1 also known as ChemR23 (Chemerin Receptor 23) is a protein that in humans is encoded by the ''CMKLR1'' gene. Chemokine receptor-like 1 is a G protein-coupled receptor for the chemoattractant adipokine chemerin and the ome ...

GPR32 G protein-coupled receptor 32, also known as GPR32 or the RvD1 receptor, is a human receptor (biochemistry) belonging to the rhodopsin-like subfamily of G protein-coupled receptors. Gene The ''GPR32'' was initially identified and defined by mo ...

FPR2 N-formyl peptide receptor 2 (FPR2) is a G-protein coupled receptor (GPCR) located on the surface of many cell types of various animal species. The human receptor protein is encoded by the ''FPR2'' gene and is activated to regulate cell function ...

, and

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...

s have been proposed to be the receptors through which these SPMs operate to

down-regulate In the biology, biological context of organisms' regulation of gene expression, production of gene products, downregulation is the process by which a cell (biology), cell decreases the quantity of a cellular component, such as RNA or protein, in r ...

TRPV3 and thereby pain perception. 2-Aminoethoxydiphenyl borate (2-APB) is a mixed agonist-antagonist of the TRPV3 receptor, acting as an antagonist at low concentrations but showing agonist activity when used in larger amounts.

Drofenine Drofenine is an antimuscarinic antispasmodic drug used for relaxing smooth muscle, thereby treating conditions, such as: dysmenorrhea, and pain in the gastrointestinal tract, biliary passages, and urogenital tract. Drofenine is assumed to work b ...

also acts as a TRPV3 agonist in addition to its other actions. Conversely,

icilin Icilin (AG-3-5) is a synthetic super-agonist of the transient receptor potential M8 (TRPM8) ion channel. Although structurally not related with menthol, it produces an extreme sensation of cold, both in humans and animals. It is almost 200 times m ...

has been shown to act as a TRPV3 antagonist, as well as a

TRPM8 Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular ...

agonist.

Forsythoside B Forsythoside B is a natural product from the phenylpropanoid glycoside group, which is found in a number of plant species such as '' Marrubium alysson'', ''Phlomis armeniaca'', '' Scutellaria salviifolia'', ''Phlomoides tuberosa'', ''Phlomoides ro ...

acts as a TRPV3 inhibitor among other actions. Farnesyl pyrophosphate is an endogenous agonist of TRPV3, while

from

frankincense Frankincense (also known as olibanum) is an aromatic resin used in incense and perfumes, obtained from trees of the genus ''Boswellia'' in the family Burseraceae. The word is from Old French ('high-quality incense'). There are several species o ...

also acts as an agonist at TRPV3. TRPV3-74a is a selective TRPV3 antagonist.

Ligands

Agonists

Cannabidiol Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. , clinical research on CBD incl ...

Tetrahydrocannabivarin Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of a pentyl (5-carbon) group on the molecule, which makes it produce very different effects from THC. ...

Cannabigerolic acid Cannabigerolic acid (CBGA) is the acidic form of cannabigerol (CBG). It is a dihydroxybenzoic acid and olivetolic acid in which the hydrogen at position 3 is substituted by a geranyl group. It is a biosynthetic precursor to Delta-9-tetrahydrocann ...

* Cannabigerovarin *

References

External links

* {{Transient receptor potential channel modulators Ion channels