TRPV Channels

TRPV channels (Transient receptor potential channels, vanilloid subtype) are members of the TRP channel superfamily; six TRPV channels have been identified (TRPV1-6). These cation channels are split into three subgroups based on their complex activation. TRPV1, TRPV2 and TRPV3 are temperature sensitive, TRPV4 senses changes in cell volume and osmolarity, and TRPV5 and TRPV6 are Ca2+ sensitive and Ca2+ selective channels. TRPV channels have been linked to a wide range of physiological processes including nociception and pain, immune response, and internal organ function.

Products
Background
Literature (2)
Gene Data

TRPV Channel Agonists

Cat. No. Product Name / Activity
1116 AM 404
TRPV agonist; also anandamide transport inhibitor
1339 Anandamide
Endogenous TRPV1 agonist; also cannabinoid agonist
0462 (E)-Capsaicin
TRPV agonist
6433 GSK 1016790A
Potent TRPV4 agonist; active in vivo
1641 OLDA
Potent and selective endogenous TRPV1 agonist
0934 Olvanil
Potent TRPV agonist
3745 RN 1747
Selective TRPV4 agonist

TRPV Channel Antagonists

Cat. No. Product Name / Activity
5781 A 425619
Potent TRPV1 antagonist
4319 A 784168
Potent and selective TRPV1 antagonist
4330 AMG 21629
Potent and selective TRPV1 antagonist
5995 AMG 517
Potent TRPV1 antagonist
2316 AMG 9810
Potent and selective TRPV1 competitive antagonist
3875 BCTC
TRPV1 antagonist
0464 Capsazepine
TRPV antagonist; also activator of ENaCδ
7199 (±)-Eriodictyol
Potent TRPV1 antagonist; also antioxidant; activates Nrf2/ARE signaling
5106 GSK 2193874
Potent and selective TRPV4 antagonist; orally active
4100 HC 067047
Potent and selective TRPV4 antagonist
3361 JNJ 17203212
Reversible, competitive and potent TRPV1 antagonist
1577 L-R4W2
TRPV1 antagonist peptide
3746 RN 1734
Selective TRPV4 antagonist
5678 RN 9893 hydrochloride
Potent and selective TRPV4 antagonist
1439 Ruthenium Red
Blocks capsaicin-activated cation channels
1615 SB 366791
Potent and selective TRPV1 competitive antagonist
3265 SB 452533
Potent TRPV1 antagonist
6990 SET 2
Selective TRPV2 antagonist
4729 α-Spinasterol
TRPV1 antagonist; active in vivo
1098 Tranilast
Antiallergic; inhibits TRPV2-mediated responses
6831 TRPV3 74a
Selective TRPV3 antagonist; brain penetrant

TRPV Channel Inhibitors

Cat. No. Product Name / Activity
7118 cis-22a
TRPV6 inhibitor

TRPV Channel Activators

Cat. No. Product Name / Activity
4876 Eact
TRPV1 activator; also TMEM16A activator

TRPV channels are so called as a result of their activation by a group of compounds known as vanilloids, which includes capsaicin, compound found in chilli peppers. Capsaicin binds to TRPV1 channels and this binding is responsible for the hot, pain-like sensation caused by eating a spicy chilli.

Like all TRP channels, TRPV channels are cation selective ion channels formed from four individual subunits. They can exist as homo or heterotetramers and display extremely complex activation mechanisms. Different TRPV channels are activated by different stimuli, such as changes in temperature, mechanical stimuli, exogenous small molecules, and endogenous molecules and lipids, such as arachidonic acid metabolites, anandamide (Cat. No. 1339) and diacylglycerol (DAG). The response to a single stimulus cannot be mapped to a single TRPV channel as each channel responds to more than one stimulus. Also, TRPV channels can form heteromultimers, giving rise to channel complexes that can be activated by a wide range of stimuli.

TRPV Receptor Subtypes

Six TRPV channel subtypes have been identified, which can be grouped by their main function; TRPV1, TRPV2 and TRPV3 are thermosensors, TRPV4 is an osmosensor, and TRPV5 and TRPV6 are Ca2+ sensitive, Ca2+ selective channels. All TRPV channels are widely expressed. TRPV1 to 4 are expressed on afferent nociceptors where they act as transducers of thermal and chemical stimuli. Blockers of these receptors may have application in the prevention and treatment of various types of pain.

Table 1: TRPV Channel Subtype Function and Stimuli

TRPV Channel Function Example Stimuli
TRPV1 Capsaicin receptor & noxious thermosensor Capsaicin, temp >43°C, resiniferatoxin, H+, anandamide
TRPV2 Osmosensor & noxious thermosensor Temp >52°C, osmotic pressure
TRPV3 Thermosensor Temp 22-39°C, camphor
TRPV4 Osmosensor & thermosensor Temp >25°C, H+, arachidonic acid metabolites, mechanical stimuli
TRPV5 Calcium-sensitive cation channel Intracellular Ca2+, constituitively active
TRPV6 Calcium-sensitive cation channel Intracellular Ca2+, constituitively active


TRPV1 is widely distributed in the peripheral and central nervous system. In the periphery TRPV1 functions as a noxious thermosensor (>43°C) and is heavily involved in detection and regulation of body temperature. TRPV1 is also activated by endogenous ligands such as anandamide (Cat. No. 1339) and NADA (Cat. No. 1568). Exogenous activators of TRPV1 include capsaicin (Cat. No. 0462), and allyl isothiocyanate found in mustard and wasabi. In the brain, TRPV1 is thought to mediate long-term depression (LTD) in the hippocampus, which is linked to a decrease in the ability to form new memories.

The sensitivity of TRPV1 to stimuli is not static; it is modulated by inflammatory mediators like bradykinin and prostaglandins. Phosphorylation of TRPV1 by protein kinase C (PKC) via phospholipase signaling pathways increases its sensitivity to noxious stimuli and may lead to hyperalgesia.

TRPV2 is most highly expressed in the lungs and spleen but is also found in the brain and in a subpopulation of large sensory neurons. This TRP channel functions as a noxious thermosensor (>52°C), although it has also been linked to many other cellular and physiological processes. In mice, TRPV2 is activated by cell stretching and hypo-osmolarity, suggesting it can also be an osmosensor, however the exact activation mechanism is yet to be discovered.

In cancer TRPV2 has a role in the negative regulation of apoptosis through the Fas/Fas ligand pathway. Overexpression of TRPV2, identified in some tumors, leads to abnormal signaling that drives unregulated cell proliferation and resistance to apoptotic stimuli. TRPV2 is also expressed on lymphocytes and myeloid cells in the immune system, where it mediates macrophage chemotaxis, cytokine releases, phagocytosis and inflammation.

In brain, TRPV2 is thought to be responsible for the anti-epileptic effects of cannabidiol (CBD; Cat. No. 1570). As well as being cannabinoid receptor agonists, plant-derived cannabinoids act as TRPV2 agonists. CBD binds to TRPV2 channels, resulting in a reduction in epileptic activity and decreased seizure incidence.

TRPV3 has wide expression but displays particularly high levels in keratinocytes in skin, where it senses warm temperatures. This ion channel is also thought to have a role in hair growth, as mutations in TRPV3 cause hair loss in mice.

TRPV4 is a thermosensor and osmosensor, which is activated by osmotic, thermal, chemical and mechanical stimuli. TRPV4 has roles in vascular function, skeleton growth and structural integrity, skin barrier function, lung and airway function, and in pain and nociception. In the brain, TRPV4 is responsible for regulating osmotic pressure. Like TRPV1, the sensitivity of TRPV4 to stimuli is modulated by inflammation and arachidonic acid metabolites. More than 50 pathogenic mutations have been described for TRPV4, associated with skeletal dysplasia, peripheral neuropathies, and neurological motor function disorders.

Both TRPV5 and TRPV6 are highly selective for Ca2+ over Na+ and are involved in reabsorption of Ca2+ across intestinal and kidney epithelia, and regulation of blood Ca2+ content. They show differing tissue expression profiles, with TRPV5 predominantly found in the distal convoluted tubule and connecting tubules of the kidney while TRPV6 displays a broader expression pattern, including the intestines, kidney, placenta, pancreas and sweat glands. Unlike the rest of the TRPV channel family, TRPV5 and TRPV6 are not thermosensitive, or activated by ligand binding; they are both constitutively open at physiological membrane potentials. They are also modulated by calmodulin binding in a Ca2+-dependent manner.

External sources of pharmacological information for TRPV Channels :

Literature for TRPV Channels

Tocris offers the following scientific literature for TRPV Channels to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


Pain

Pain Research Product Guide

A collection of over 280 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
Pain

Pain Poster

Peripheral sensitization is the reduction in the threshold of excitability of sensory neurons that results in an augmented response to a given external stimulus. This poster outlines the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. The role of ion channels, GPCRs, neurotrophins, and cytokines in sensory neurons are also described.

TRPV Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
TRPV1 Human TRPV1 NM_018727 Q8NER1
Mouse Trpv1 NM_001001445 Q704Y3
Rat Trpv1 NM_031982 O35433
TRPV2 Human TRPV2 NM_016113 Q9Y5S1
Mouse Trpv2 NM_011706 Q9WTR1
Rat Trpv2 NM_017207 Q9WUD2
TRPV3 Human TRPV3 NM_145068 Q8NET8
Mouse Trvp3 NM_145099 Q8K424
Rat Trpv3 NM_001025757 Q4QYD9
TRPV4 Human TRPV4 NM_021625 Q96Q92
Mouse Trpv4 NM_022017 Q9EPK8
Rat Trpv4 NM_023970 Q9ERZ8
TRPV5 Human TRPV5 NM_019841 Q9NQA5
Mouse Trpv5 NM_001007572 P69744
Rat Trpv5 NM_053787 Q9JIP0
TRPV6 Human TRPV6 NM_014274 Q9H1D0
Mouse Trpv6 NM_022413 Q91WD2
Rat Trpv6 NM_053686 Q9R186

TRPV Pharmacological Data

Receptor
(other names)
TRPV1
VR1, OTRPC1, Vanilloid/capsaicin receptor
TRPV2
VRL-1, OTRPC2, GRC
TRPV3
VRL-3
TRPV4
VRL-2, OTRPC4, VR-OAC, TRP12
TRPV5
OTRPC3, ECaC, ECaC1, CaT2
TRPV6
ECaC2, CaT1, CaT-L
Description Vanilloid receptor, noxious thermosensor, non-selective cation channel Noxious heat, noxious thermosensor, non-selective cation channel Warmth sensor, moderately selective Ca2+ channel Osmosensor, moderately selective Ca2+ channel Highly selective Ca2+ channel Highly selective Ca2+ channel
Receptor distribution Dorsal root and trigeminal ganglia, brain, spinal cord, pancreas, skin epithelial, bladder Dorsal root and trigeminal ganglia, brain, spinal cord, spleen, lung, mast cells, vascular smooth muscle Brain (cortex, thalamus), skin, hair follicles, tongue, stomach, spinal cord, superior clavicular, dorsal root and trigeminal ganglia Brain, liver, kidney, adipose tissue, heart, testis, salivary gland, trachea Intestine, kidney, placenta, brain Kidney, intestine
Tissue Function Pain sensation, vasodilation Thermal pain sensation, mast cell function Putative warm sensation Osmolarity sensing with thermal modulation Active Ca+ (re)absorption Active Ca2+ (re)absorption
Key Activators Capsaicin (0462)
Resiniferatoxin (1137)
Anandamide (1339)
Olvanil (0934)
Heat (threshold ~ 43oC)
Protons
Ethanol
Noxious heat (threshold =52oC)
IGF-1
Increasing temperature (~35oC) Reduced osmolarity None (constitutively active) None (constitutively active)
Antagonists Capsazepine (0464)
5'-Iodoresiniferatoxin (1362)
Ruthenium red (1439)
JNJ 17203212 (3361)
AMG 9810 (2316)
PIP2
Ruthenium red (1439)
SKF 963365 (1147)
La3+
Ruthenium red (1439) Ruthenium red (1439) Ruthenium red (1439)
La3+
Ruthenium red (1439)
La3+

References

Gunthorpe et al (2002) The diversity in the vanilloid (TRPV) receptor family of ion channels. TiPS 23 183. Clapham et al (2003) International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels; transient receptor potential channels. Pharmacol.Rev. 55 591. Alexander et al (2004) Guide to receptors and channels. Br.J.Pharmacol. 141 S89.