Role of Transient Receptor Potential Vanilloid 1 in Inflammation and Autoimmune Diseases 英文参考文献.docVIP

Pharmaceuticals 2012, 5, 837-852; doi:10.3390/ph5080837 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Role of Transient Receptor Potential Vanilloid 1 in Inflammation and Autoimmune Diseases Fumio Tsuji * and Hiroyuki Aono Research and Development Center, Santen Pharmaceutical Co., Ltd., 8916-16 Takayama-cho, Ikoma, Nara 630-0101, Japan; E-Mail: aonoh@santen.co.jp (H.A.) * Author to whom correspondence should be addressed; E-Mail: fumio.tsuji@santen.co.jp; Tel.: +81-743-79-4552; Fax: +81-743-79-4518. Received: 29 June 2012; in revised form: 2 August 2012 / Accepted: 15 August 2012 / Published: 17 August 2012 Abstract: Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is a receptor activated by high temperatures and chemical agonists such as the vanilloids and protons. Because of these properties, TRPV1 has emerged as a polymodal nocisensor of nociceptive afferent neurons. TRPV1 is thought to be a central transducer of hyperalgesia and a prime target for controlling pain pharmacologically because it is a point where many proalgesic pathways converge and it is upregulated and sensitized by inflammation and injury. However, whether TRPV1 agonists promote or inhibit inflammation remains unclear. We recently demonstrated that SA13353 (1-[2-(1- adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea), a novel TRPV1 agonist, inhibits tumor necrosis factor-? production by the activation of capsaicin-sensitive afferent neurons and reduces the severity of symptoms in kidney injury, lung inflammation, arthritis, and encephalomyelitis. These results suggest that TRPV1 agonists may act as anti-inflammatories in certain inflammatory and autoimmune conditions in vivo. Given the potential deleterious effects of inhibiting the population of channels with a protective function, caution shoul