TRPV is a family of
transient receptor potential
Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TR ...
cation channels (TRP channels) in animals. All TRPVs are highly calcium selective.
TRP channels are a large group of
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s consisting of six protein families, located mostly on the
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
of numerous human and animal cell types, and in some fungi.
TRP channels were initially discovered in the ''trp'' mutant strain of the fruit fly ''
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' that displayed transient elevation of potential in response to light stimuli, and were therefore named "transient receptor potential" channels. The name now refers only to a family of proteins with similar structure and function, not to the mechanism of their activation. Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. There are about 28 TRP channels that share some structural similarity to each other.
These are grouped into two broad groups: group 1 includes
TRPC
TRPC is a family of transient receptor potential cation channels in animals.
TRPC channels form the subfamily of channels in humans most closely related to drosophila TRP channels. Structurally, members of this family possess a number of similar ...
( "C" for canonical), TRPV ("V" for
vanilloid
The vanilloids are compounds which possess a vanillyl group. They include vanillyl alcohol, vanillin, vanillic acid, acetovanillon, vanillylmandelic acid, homovanillic acid, capsaicin, etc. Isomers are the isovanilloids.
:
A number of vanilloi ...
),
TRPM
TRPM is a family of transient receptor potential ion channels (''M'' standing for '' wikt:melastatin''). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8.
Unlike the TRPC ...
("M" for melastatin),
TRPN TRPN is a member of the transient receptor potential channel family of ion channels, which is a diverse group of proteins thought to be involved in mechanoreception. The TRPN gene was given the name ''no mechanoreceptor potential C'' (''nompC'') wh ...
and
TRPA. In group 2 there are
TRPP
TRPP (transient receptor potential polycystic) is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease.
Subcategories
TRPP subunits can be divided into two subcategories depending on structu ...
("P" for polycystic) and
TRPML
TRPML (transient receptor potential cation channel, mucolipin subfamily) comprises a group of three evolutionarily related proteins that belongs to the large family of transient receptor potential ion channels. The three proteins TRPML1, TRPML2 ...
("ML" for mucolipin).
Structure
Functional TRPV ion channels are
tetramer
A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...
ic in structure and are either homo-tetrameric (four identical subunits) or hetero-tetrameric (a total of four subunits selected from two or more types of subunits). The four subunits are symmetrically arranged around the ion conduction pore. Although the extent of heteromerization has been the subject of some debate, the most recent research in this area suggest that all four thermosensitive TRPVs (1-4) can form heteromers with each other. This result is in line with the general observation that TRP coassembly tends to occur between subunits with high sequence similarities. How TRP subunits recognize and interact with each other is still poorly understood.
The TRPV channel
monomer
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
Mo ...
ic subunit components each contain six
transmembrane
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
(TM)
domains (designated S1–S6) with a pore domain between the fifth (S5) and sixth (S6) segments.
TRPV subunits contain three to five
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
ankyrin repeats
Ankyrins are a family of proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral mem ...
.
Function
TRPV proteins respond to the taste of garlic (
allicin
Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...
).
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 ...
contributes to heat and inflammation sensations and mediates the pungent odor and pain sensations associated with
capsaicin
Capsaicin (8-methyl-''N''-vanillyl-6-nonenamide) ( or ) is an active component of chili peppers, which are plants belonging to the genus ''Capsicum''. It is a chemical irritant for mammals, including humans, and produces a sensation of burning ...
and
piperine
Piperine, along with its isomer chavicine, is the alkaloid responsible for the pungency of black pepper and long pepper. It has been used in some forms of traditional medicine.
Preparation
Due to its poor solubility in water, piperine is typica ...
.
Family members
The table below summarizes the functions and properties of the individual TRPV channel family members:
Clinical significance
Mutations in TRPs have been linked to
neurodegenerative
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
disorders, skeletal
dysplasia
Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...
, kidney disorders,
and may play an important role in cancer. TRPs may make important therapeutic targets. There is significant clinical significance to TRPV1, TRPV2, and TRPV3's role as thermoreceptors, and TRPV4's role as mechanoreceptors; reduction of chronic pain may be possible by targeting ion channels involved in thermal, chemical, and mechanical sensation to reduce their sensitivity to stimuli.
For instance, the use of TRPV1 agonists would potentially inhibit
nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, co ...
at TRPV1, particularly in pancreatic tissue where TRPV1 is highly expressed.
The TRPV1 agonist capsaicin, found in chili peppers, has been indicated to relieve neuropathic pain.
TRPV1 antagonists inhibit nociception at TRPV1.
Role in cancer
Altered expression of TRP proteins often leads to
tumorigenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
, clearly seen in TRPM1.
Particularly high levels of TRPV6 in prostate cancer have been noted. Such observations could be helpful in following cancer progression and could lead to the development of drugs over activating ion channels, leading to
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
and
necrosis
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
. Much research remains to be done as to whether TRP channel mutations lead to cancer progression or whether they are associated mutations.
As drug targets
Four TRPVs (TRPV1, TRPV2, TRPV3, and TRPV4) are expressed in
afferent nociceptor
A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...
s, pain sensing neurons, where they act as transducers of thermal and chemical stimuli. Agonists, antagonists, or modulators of these channels may find application for the prevention and treatment of pain.
A number of TRPV1 selective blockers such as
resiniferatoxin
Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge (''Euphorbia resinifera''), a cactus-like plant commonly found in Morocco, and in '' Euphorbia poissonii'' found in northern Nigeria. are currently in
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s for the treatment of various types of pain.
See also
*
Discovery and development of TRPV1 antagonists
*
TRPA1
Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the ''TRPA1'' (and in mice and rats by the ''Trpa1' ...
References
External links
*
*
*
{{Transient receptor potential channel modulators
Membrane proteins
Ion channels