Author:

Keywords:

root ganglion neurons, epithelial ca2+ channel, high-affinity antagonists, primary sensory neurons, activated ion-channel, capsaicin-receptor, trp channels, in-vivo, plasma-membrane, protease-activated-receptor-2 sensitizes, Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, EPITHELIAL CA2+ CHANNEL, HIGH-AFFINITY ANTAGONISTS, ROOT GANGLION NEURONS, GATED ION-CHANNEL, CAPSAICIN-RECEPTOR, SENSORY NEURONS, TRP CHANNELS, PROTEASE-ACTIVATED-RECEPTOR-2 SENSITIZES, MECHANICAL HYPERALGESIA, BIARYL CARBOXAMIDES, Animals, Binding Sites, Humans, Ligands, Phylogeny, TRPV Cation Channels, 0601 Biochemistry and Cell Biology, 1109 Neurosciences, 1115 Pharmacology and Pharmaceutical Sciences, 3101 Biochemistry and cell biology, 3214 Pharmacology and pharmaceutical sciences

Abstract:

Depending on their primary structure, the 28 mammalian transient receptor potential (TRP) cation channels identified so far can be sorted into 6 subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPP ("Polycystin"), TRPML ("Mucolipin"), and TRPA ("Ankyrin"). The TRPV subfamily (vanilloid receptors) comprises channels critically involved in nociception and thermosensing (TRPV1, TRPV2, TRPV3, and TRPV4), whereas TRPV5 and TRPV6 are involved in renal Ca2+ absorption/reabsorption. Apart from TRPV1, the pharmacology of these channels is still insufficiently known. Furthermore, only few small-molecule ligands for non-TRPV1 vanilloid receptors have been identified, and little is known of their endogenous ligands, resulting in a substantial "orphan" state for these channels. In this review, we summarize the pharmacological properties of members of the TRPV subfamily, highlighting the critical issues and challenges facing their "deorphanization" and clinical exploitation.