Capsaicin receptor

Capsaicin receptor" agonists capsaicin, resmiferatoxin II, Via voltage-gated channels maitotoxm ( ) OH ... 

Capsaicin, also known as N-Vanillyl-8-methyl-6-(E)-noneamide, is the most pungent of the group of compounds called capsaicinoids It is a common ingredient in varieties of pepper such as habanero, Thai, tabasco, cayenne etc. One target with which capsaicin interacts is the capsaicin receptor, an ion channel belonging to the superfamily of TRP channels. Because of the structural relation to other TRP channels and because the vanilloid moiety is an essential component of capsaicin, the capsaicin receptor is also called TRPVI or vanilloid receptor (VR1). It is involved in heat and pain perception. 

These are a subset of sensory neurons having their cell bodies (small to medium size) in dorsal root and in cranial nerve ganglia and possessing nonmyelinated (C-type) or thinly myelinated (A-delta type) fibres. This subset of neurons express transient receptor potential vanilloid type 1 (TRPV1, or vanilloid, or capsaicin receptor) that is excited by capsaicin, the pungent ingredient of chilli. These neurons have been classified as polymodal nociceptors because they can be excited by various noxious stimuli. 

In 1990, specific binding of [ H]resiniferatoxin (2, RTX), an ultrapotent capsaicin analogue isolated from the latex of the cactus-like plant Euphorbia resinifera, provided the first direct proof for the existence of a distinct capsaicin receptor [4]. Based on the chemical motif (a vanillyl moiety) shared by (1) and (2), this receptor was termed the vanilloid receptor VRl [1]. 

Caterina et al. The capsaicin receptor a heat-activated ion channel in the pain pathway. Nature 389, 1997. 

Szallasi A, Blumberg PM. (1999). Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 51(2) 159-212. 

Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Juhus D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21 531-543... 

Birds may have a trigeminal receptor for o-aminoacetophenone and methyl anthranilate, analogous to the capsaicin receptor in mammals (Clark and Shah, 1994). 

Nagy I, Santha P, Jancso G, Urban L, The role of the vanilloid (capsaicin) receptor (TRPVl) in physiology and pathology, Eur J Pharmacol 500 351-369, 2004. 

Tominaga, M., Wada, M., Masu, M. Potentiation of capsaicin receptor activity by metabotropic ATP... 

Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., Julius, D. The capsaicin receptor a heat-activated ion channel in the pain pathway, Nature 1997, 389, 816-824. 

Helliwell, R.J., McLatchie, L.M., Clarke, M., Winter, J., Bevan, S., McIntyre, P. Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia, Neurosci. Lett. 1998, 250, 177-180. 

Schumacher, M.A., Moff, I., Sudanagunta, S.P., Levine, J.D. Molecular cloning of an N-terminal splice variant of the capsaicin receptor. Loss of N-terminal domain suggests functional divergence among capsaicin receptor subtypes, J. Biol. Chem., 2000, 275, 2756-2762. 

Szallasi, A. Autoradiographic visualization and pharmacological characterization of vanilloid (capsaicin) receptors in several species, including man, Acta Physiol. Scand. 1995 (Suppl.), 629,1-68. 

Szallasi, A. and Blumberg, P.M. Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor, Life Sci. 1990b, 47,1399-1408. 

Caterina, M. J., M. A. Schumacher, M. Tominaga, T. A. Rosen, J. D. Levine and D. Julius, 1997, The capsaicin receptor a heat-activated ion channel in the pain pathway, Nature, 389, (6653), pp. 816-824 Chuang, H. H., W. M. Neuhausser and D. Julius, 2004, The Super-Cooling Agent Icilin Reveals a Mechanism of Coincidence Detection by a Temperature-Sensitive TRP Channel, Neuron, 43, (6), pp. 859-869... 

Chuang, H. H., E. D. Prescott, H. Kong, S. Shields, S. E. Jordt, A. I. Basbaum, M. V. Chao and D. Julius, 2001, Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition, Nature, 411, (6840), pp. 957-962... 

Wang, X., Miyares, R. L., and Ahem, G. P. (2005). Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J. Physiol. 564, 541-547. 

These findings might be explained by the observation that 5-HT3A-R are expressed mostly on myelinated A5 afferents and a unique population of C fibers, few of which coexpress the vanilloid/capsaicin receptor VR1 or the proedema factor substance P (137). Consistent with this expression pattern, deep dorsal hom neurons in the KOs fire at a lower rate than those of control animals during exposure to nociceptive stimuli. 

Daphnanes (C5 (C7 C6) include a variety of cytotoxic, irritant, inflammatory and toxic compounds from the Thymelaeaceae and the Euphorbiaceae. Of particular note are the highly inflammatory PKC activators resiniferatoxin and tinyatoxin from Euphorbia species (Euphorbiaceae) and thymeleatoxin from Thymeka hirsuta (Thymelaeaceae). While the nonester resiniferonol is inactive, the ester (X—CO—O—Y) resiniferatoxin is both an anti-nociceptive vanilloid receptor (capsaicin receptor) agonist and a PKC activator, as is the ester tinyatoxin. 

Szolcsanyi J (2000) Are cannabinoids endogenous ligands for the VRl capsaicin receptor Trends Pharmacol Sci 21 41-42... 

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