Zer, Institute of Experimental and Clinical Pharmacology, Health-related University of Graz, Universitatsplatz four, A-8010 Graz, Austria. E-mail: [email protected] Received 29 April 2008; revised 18 June 2008; accepted 20 August 2008; published on the net 22 SeptemberThe pharmacological challenge of TRPV1 P HolzerTable 1 Overview of TRP channels, N-Glycolylneuraminic acid Data Sheet expressed by sensory neurones or cells associated with sensory neurones which are involved in nociception, thermosensation and chemaesthesis TRP channel TRPV1 Discomfort modality Heat Acidosis Chemaesthetic (irritant) pain Heat Chemaesthetic (irritant) discomfort Acidosis Cold Chemaesthetic (irritant) pain Chemaesthetic (irritant) discomfort Thermosensation 442 1C Chemaesthesis Capsaicin (red pepper), resiniferatoxin (Euphorbia), gingerol and zingerone (ginger), piperine (black pepper), eugenol (clove), camphor, vanillatoxins 1-3 (Tarantula), ethanol, acid (pHo6) D9-tetrahydrocannabinol (D9-THC) Carvacrol (oregano), eugenol, thymol (thyme), vanillin (vanilla), camphor, menthol (mint) Acid (pHo6) Menthol, icilin, geraniol, L-carvone, isopulegol, linalool Allicin and diallyl disulphide (garlic), allyl isothiocyanate (mustard, horseradish, wasabi), cinnamaldehyde (cinnamon), carvacrol, gingerol, eugenol, icilin, acrolein, formaldehyde, methyl salicylate, D9-THCTRPV2 TRPV3 TRPV4 TRPM8 TRPA452 1C 433 1C (warmth) 4254 1C (warmth) o25 1C o17 1CThe thermo- and chemosensory properties referred to possess been delineated by studying heterologously expressed TRP channels. The list of chemicals activating TRP channels will not be comprehensive. For references see Dhaka et al. (2006) and Bandell et al. (2007).re-named transient receptor prospective vanilloid-1 (TRPV1), which stands for transient receptor potential vanilloid-1 (Caterina and Julius, 2001; Clapham et al., 2005). The story of TRPV1, however, had begun half a century ago, when the peculiar pharmacology of capsaicin was very first revealed. Responsible for the pungency of red pepper (Capsicum spp.), the vanilloid capsaicin in its pure type is among the most painful chemical substances we know, conveying the sensation of `hot’ and `burning’. It was the Hungarian pharmacologist Nicolas Jancso who 1st recognized that capsaicin acts especially on nociceptive afferent neurones (Jancso, 1960). Further function by two eminent Hungarian study groups in Szeged and Pecs supplied compelling evidence that the selectivity of capsaicin’s action on afferent neurones can only be accounted for by an action on distinct capsaicin receptors (Szolcsanyi and Jancso-Gabor, 1975; Jancso et al., 1977, 1987; Szolcsanyi, 1982, 2004; Nagy et al., 2004). The discovery of particular vanilloid-binding internet sites (Szallasi and Blumberg, 1999) along with a selective capsaicin antagonist (Bevan et al., 1992) were additional vital measures towards the identification of TRPV1 as the capsaicin receptor. Therapeutic opportunities were envisaged from the structure ctivity relationship for the pain-producing impact of capsaicin (Szolcsanyi and Jancso-Gabor, 1975) and its axonal web-site of action following regional administration to afferent neurones (Jancso et al., 1980). TRPV1 was quickly to be joined by other TRP channels with exceptional sensory modalities. The group of thermo-TRP channels is able to sense the whole spectrum of temperatures from painful cold to painful heat (Dhaka et al., 2006). Moreover, they are in a position to detect specific chemical entities which includes unpleasant and/or painful toxins, whereby TRP channels subserve chemaesthesis, the chemical sen.
