Cloning and functional expression of a human orthologue of rat vanilloid receptor-1.
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.
Hayes
Philip
P
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.
Meadows
Helen J
HJ
Gunthorpe
Martin J
MJ
Harries
Mark H
MH
Duckworth
Malcolm D
MD
Cairns
William
W
Harrison
David C
DC
Clarke
Catherine E
CE
Ellington
Kathryn
K
Prinjha
Rab K
RK
Barton
Amanda J L
AJL
Medhurst
Andrew D
AD
Smith
Graham D
GD
Topp
Simon
S
Murdock
Paul
P
Sanger
Gareth J
GJ
Terrett
John
J
Jenkins
Owen
O
Benham
Christopher D
CD
Randall
Andrew D
AD
Gloger
Isro S
IS
Davis
John B
JB
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002875:Chromosomes / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011955:Receptors, Drug / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D050916:TRPV Cation Channels; D013696:Temperature; D014981:Xenopus
D012333:RNA, Messenger; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D004247:DNA