Cortright D N, Crandall M, Sanchez J F, Zou T, Krause J E, White G
Department of Biochemistry, Neurogen Corporation, 35 N.E. Industrial Road, Branford, Connecticut, 06405, USA.
Biochem Biophys Res Commun. 2001 Mar;281(5):1183-9. doi: 10.1006/bbrc.2001.4482.
The irritant action of capsaicin is mediated by the vanilloid receptor, VR1, which is expressed in sensory neurons termed nociceptors. Capsaicin also desensitizes nociceptors and, thus, is useful clinically as an analgesic. Given the potential importance of VR1 in pain, we have cloned the human capsaicin receptor, hVR1, from a human dorsal root ganglia (DRG) cDNA library. Human VR1 protein is 85% identical to the rat VR1 and many of the amino acid differences are concentrated at the amino and carboxyl termini. VR1 is expressed in DRG as an approximately 4.2 kilobase RNA, and is also expressed in the central nervous system and in the kidney. Capsaicin (EC(50) = 853 nM), low pH (<5.5), and noxious heat (44 degrees C) activate hVR1 expressed in Xenopus oocytes. Subthreshold pH (6.4) sensitizes VR1 to capsaicin (EC(50) = 221 nM). This study demonstrates the similarity of human and rat VR1 in integrating multiple noxious stimuli.
辣椒素的刺激作用由香草酸受体VR1介导，该受体在称为伤害感受器的感觉神经元中表达。辣椒素还能使伤害感受器脱敏，因此在临床上可用作镇痛药。鉴于VR1在疼痛中的潜在重要性，我们从人背根神经节（DRG）cDNA文库中克隆了人辣椒素受体hVR1。人VR1蛋白与大鼠VR1的同源性为85%，许多氨基酸差异集中在氨基和羧基末端。VR1在DRG中以约4.2千碱基的RNA形式表达，在中枢神经系统和肾脏中也有表达。辣椒素（EC50 = 853 nM）、低pH值（<5.5）和有害热（44℃）可激活非洲爪蟾卵母细胞中表达的hVR1。阈下pH值（6.4）使VR1对辣椒素敏感（EC50 = 221 nM）。本研究证明了人和大鼠VR1在整合多种有害刺激方面的相似性。
