大鼠香草酸受体-1人类同源物的克隆与功能表达

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

作者信息

Hayes Philip, Meadows Helen J, Gunthorpe Martin J, Harries Mark H, Duckworth Malcolm D, Cairns William, Harrison David C, Clarke Catherine E, Ellington Kathryn, Prinjha Rab K, Barton Amanda J L, Medhurst Andrew D, Smith Graham D, Topp Simon, Murdock Paul, Sanger Gareth J, Terrett John, Jenkins Owen, Benham Christopher D, Randall Andrew D, Gloger Isro S, Davis John B

机构信息

Department of Biotechnology and Genetics, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK Department of Bioinformatics, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK.

出版信息

Pain. 2000 Nov;88(2):205-215. doi: 10.1016/S0304-3959(00)00353-5.

DOI:10.1016/S0304-3959(00)00353-5

PMID:11050376

Abstract

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.

摘要

辣椒素、树脂毒素、质子或热已被证明可激活一种离子通道，称为大鼠香草酸受体-1（rVR1），最初是通过表达克隆针对辣椒素敏感表型分离得到的。在此，我们描述了人类香草酸受体-1（hVR1）cDNA的克隆，其包含一个2517 bp的开放阅读框，编码一种与大鼠香草酸受体-1具有92%同源性的蛋白质。表达该cDNA的卵母细胞或哺乳动物细胞通过产生内向膜电流对辣椒素、pH值和温度作出反应。转染了人类VR1的哺乳动物细胞对辣椒素的反应是细胞内钙增加。人类VR1的染色体定位在17p13，在人类背根神经节中表达，并且在广泛的中枢神经系统和外周组织中也有低水平表达。序列同源性、相似的表达谱和功能特性共同证实，克隆的cDNA代表大鼠VR1的人类同源物。