Cloning and functional expression of a human orthologue of... : PAIN (original) (raw)

Article

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

Hayes, Philipa; Meadows, Helen J.b; Gunthorpe, Martin J.b; Harries, Mark H.b; Duckworth, Malcolm D.c; Cairns, Williama; Harrison, David C.b; Clarke, Catherine E.b; Ellington, Kathryna; Prinjha, Rab K.b; Barton, Amanda J.L.b; Medhurst, Andrew D.b; Smith, Graham D.b; Topp, Simonc; Murdock, Paula; Sanger, Gareth J.b; Terrett, Johna; Jenkins, Owena; Benham, Christopher D.b; Randall, Andrew D.b; Gloger, Isro S.a; Davis, John B.b,*

a_Department of Biotechnology and Genetics, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK_

b_Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK_

c_Department of Bioinformatics, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow CM19 5AW, UK_

*Corresponding author. Tel.: +44-1279-622-601; fax: +44-1279-622-555

E-mail: [email protected]

Received 12 November 1999; received in revised form 17 May 2000; accepted 12 June 2000.

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.