Editorial [Hot Topic: New Potential Therapies from Vanilloid Transient Receptor Cation (TRPV) Channels (Executive Editors: V. Di Marzo and K. Starowicz)]

In this issue of Current Pharmaceutical Design the superfamily of TRP (Transient Receptor Potential) cation channels is the subject of four detailed reviews. A variety of more than 30 cation channels, members of the TRP family, permeable to Ca2+ and other cations are involved in several pathological and physiological conditions. Based on sequence homology, this superfamily of cation channels has been divided in six main subfamilies: canonical (TRPC), vanilloid (TRPV), melastatin (TRPM), polycystin (TRPP), mucolipin (TRPML) and the ankyrin (TRPA). The search for the molecular targets for naturally occurring substances, especially of plant origin, and studies of the mechanism of the transduction of physical stimuli such as temperature, mechanical pressure and light, have allowed the characterization and classification of many TRP channels. In fact, attempts to understand the molecular mechanism of action of the pro-nociceptive effects of vanillyl moietycontaining compounds such as capsaicin, the pungent component of hot chilli peppers (from Capsicum sp.), or its potent analogue resiniferatoxin (RTX, from Euphorbia sp.), led to the cloning of the “vanilloid” receptor (TRPV1) already 10 years ago, and of other heatsensitive TRPV channels soon thereafter. More recently, TRP channels sensitive to low temperatures, such as TRPM1 and TRPA1, have also been identified. While celebrating the first decennium of TRPV1 research, one should bear in mind that in addition to its expression in primary sensory afferents and its well documented biological role in pain perception, a significant number of studies have been published indicating that functionally active populations of TRPV1 receptors are expressed also in the central nervous system (CNS), thus suggesting that they are involved in many more functions than just nociception. The four reviews in this issue of the journal highlight and discuss some important aspects of TRP channel-related issues. Appendino and colleagues [1] provide an overview of the role that natural products have played in the identification of TRP channels and of their function as possible candidates for drug discovery. Vennekens and coworkers [2] summarize the fundamental properties of all members of the TRPV subfamily (TRPV1- TRPV6), in the light of their multi-faceted cellular functions, expression, molecular structure, regulation and pharmacology. The subsequent review by Gunthorpe and Szallasi [3] focusses on the function and potential therapeutic exploitation of TRPV1 channels located in the peripheral nervous system. The authors discuss the role of TRPV1 not only in pain but also in cancer, obesity and diabetes, among others, and the clinical development of TRPV1 agonists and antagonists. The issue of TRPV1 as a potential target in non-neuronal tissues is also reviewed. Finally, Starowicz, Cristino and Di Marzo [4] discuss current ‘hot’ data on the functional significance of TRPV1 channels in the brain, where these receptors are unlikely to be activated by irritant or noxious stimulus like high temperature or low pH, hence implying the existence of “endovanilloids”. Starowicz and colleagues focus not only on the role of potential endovanilloids in central aspects of pain control, but also on the regulation of body temperature, cardiovascular and respiratory functions, emesis, anxiety and locomotion. The common intention to all authors is to provide the reader with the most up-to-date and state-of-the-art aspects of TRP, and particularly TRPV, function under both physiological and pathological conditions, and emphasize the potential of TRP targeting for therapeutic purposes. References [1] Appendino G, Minassi A, Pagani A, Ech-Chahad A. The Role of Natural Products in the Ligand Deorphanization of TRP Channels. Curr Pharm Des 2008; 14(1): 2-17. [2] Vennekens R, Owsianik G, Nilius B. Vanilloid Transient Receptor Potential Cation Channels: An Overview. Curr Pharm Des 2008; 14(1): 18-31. [3] Gunthorpe MJ, Szallasi A. Peripheral TRPV1 Receptors As Targets for Drug Development: New Molecules and Mechanisms. Curr Pharm Des 2008; 14(1): 32-41. [4] Starowicz K, Cristino L, Di Marzo V. TRPV1 Receptors in the Central Nervous System: Potential for Previously Unforeseen Therapeutic Applications. Curr Pharm Des 2008; 14(1): 42-54.