Vanilloid, 222 receptor

Szallasi A, Cortright DN, Blum CA et al (2007) The vanilloid receptor TRPV1 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6 357-372... 

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. 

TRPVl, also known as the capsaicin- or vanilloid-receptor, is a nonselective cation channel expressed e.g., in neurons of the dorsal root and trigeminal ganglions, which integrates multiple pain-producing stimuli including heat, protons, capsaicin, and resiniferatoxin. In addition, TRPVl currents can be activated by ananda-mide, protein kinase C (PKC), and by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). 

Clinically Useful Vanilloid Receptor TRPVl Antagonists Just around the Corner (or too Early to Tell) ... 

CLINICALLY USEFUL VANILLOID RECEPTOR TRPVl ANTAGONISTS... 

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]. 

Fig. 4.1 Topological organization of the vanilloid receptor TRP VI. Highlighted are the molecular determinants of TRPVl regulation, such as recognition (binding) domains for capsaicin and acids, and phosphorylation sites for protein kinases. Numbers designate the key amino acid residues deduced from the rTRPVl primary sequence. Adapted from Ferrer-Montaniel, A. et al. (2004) Fur. J. Biochem. 271, 1820—1826.

The first vanilloid receptor antagonist was Ruthenium Red (RR), an inorganic dye [1, 2]. Commercial RR is a mixture of compounds [65] and it remains to be understood... 

The Transient Receptor Potential Vanilloid 1 (TRPVl) (vanilloid receptor 1)... 

The structure-activity relationships for thiourea derivatives have been investigated as vanilloid receptor antagonist,216 220 and mast cell leukotriene release, etc.221 224... 

Lyall, V. et al. The mammalian amiloride-insensitive nonspecific salt taste receptor is a vanilloid receptor-1 variant. /. Physiol. 558 147-159, 2004. 

Activation of vanilloid receptors by capsaicin results in a release of several neuropeptides, among which is the neurokinin substance P. Substance P normally signals pain in nociceptive afferents, so capsaicin creates a false pain/burning sensation even though no actual tissue damage occurs. General Effects... 

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