Cloning and functional expression of a human orthologue of rat vanilloid receptor-1

被引:240
作者
Hayes, P
Meadows, HJ
Gunthorpe, MJ
Harries, MH
Duckworth, DM
Cairns, W
Harrison, DC
Clarke, CE
Ellington, K
Prinjha, RK
Barton, AJL
Medhurst, AD
Smith, GD
Topp, S
Murdock, P
Sanger, GJ
Terrett, J
Jenkins, O
Benham, CD
Randall, AD
Gloger, IS
Davis, JB
机构
[1] SmithKline Beecham Pharmaceut, Dept Neurosci Res, Harlow CM19 5AW, Essex, England
[2] SmithKline Beecham Pharmaceut, Dept Biotechnol & Genet, Harlow CM19 5AW, Essex, England
[3] SmithKline Beecham Pharmaceut, Dept Bioinformat, Harlow CM19 5AW, Essex, England
关键词
capsaicin; protons; pH; temperature; nociception;
D O I
10.1016/S0304-3959(00)00353-5
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Capsaicin, resiniferatoxin, protons or heat have been shown to activate an ion channel, termed the rat vanilloid receptor-1 (rVR1), originally isolated by expression cloning for a capsaicin sensitive phenotype. Here we describe the cloning of a human vanilloid receptor-1 (hVR1) cDNA containing a 2517 bp open reading frame that encodes a protein with 92% homology to the rat vanilloid receptor-1. Oocytes or mammalian cells expressing this cDNA respond to capsaicin, pH and temperature by generating inward membrane currents. Mammalian cells transfected with human VR1 respond to capsaicin with an increase in intracellular calcium. The human VR1 has a chromosomal location of 17p13 and is expressed in human dorsal root ganglia and also at low levels throughout a wide range of CNS and peripheral tissues. Together the sequence homology, similar expression profile and functional properties confirm that the cloned cDNA represents the human orthologue of rat VR1. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:205 / 215
页数:11
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