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Cloning and functional expression of a human orthologue of rat vanilloid receptor-1
Philip Hayes1, Helen J Meadows, Martin J Gunthorpe
1Department 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.
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.