Pharmacological differences between the human and rat vanilloid receptor 1 (VR1)

• Published in: British journal of pharmacology Vol. 132; no. 5; pp. 1084 - 1094
• Main Authors: McIntyre, Peter, McLatchie, Linda M, Chambers, Anne, Phillips, Elsa, Clarke, Melanie, Savidge, Jonathan, Toms, Christy, Peacock, Marcus, Shah, Kirti, Winter, Janet, Weerasakera, Natasha, Webb, Mike, Rang, Humphrey P, Bevan, Stuart, James, Iain F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2001; Nature Publishing
• Subjects: Amino Acid Sequence - genetics; Animals; Biological and medical sciences; Calcium - metabolism; Capsaicin; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; capsazepine; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; CHO Cells; Cricetinae; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; heat activation; Hot Temperature; Humans; Hydrogen-Ion Concentration; Indicators and Reagents - pharmacology; intracellular calcium; Miscellaneous; Molecular and cellular biology; Molecular Sequence Data; pain response; Phorbol Esters - pharmacology; proton activation; Rats; Receptors, Drug - drug effects; Receptors, Drug - genetics; Receptors, Drug - metabolism; Ruthenium Red - pharmacology; Species Specificity; Vertebrates: nervous system and sense organs; VR1; Xenopus; Human; Spinal cord; Rat; Capsaicin; Interspecific comparison; Rodentia; Central nervous system; Posterior spinal horn; In vitro; CHO cell line; Vertebrata; Mammalia; Animal; Antagonist; Recombinant protein; Biological receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703918

Vanilloid receptors (VR1) were cloned from human and rat dorsal root ganglion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (CHO) cells. Both rat and human VR1 formed ligand gated channels that were activated by capsaicin with similar EC50 values. Capsaicin had a lower potency on both channels, when measured electrophysiologically in oocytes compared to CHO cells (oocytes: rat=1.90±0.20 μM; human=1.90±0.30 μM: CHO cells: rat=0.20±0.06 μM; human=0.19±0.08 μM). In CHO cell lines co‐expressing either rat or human VR1 and the calcium sensitive, luminescent protein, aequorin, the EC50 values for capsaicin‐induced responses were similar in both cell lines (rat=0.35±0.06 μM, human=0.53±0.03 μM). The threshold for activation by acidic solutions was lower for human VR1 channels than that for rat VR1 (EC50 pH 5.49±0.04 and pH 5.78±0.09, respectively). The threshold for heat activation was identical (42°C) for rat and human VR1. PPAHV was an agonist at rat VR1 (EC50 between 3 and 10 μM) but was virtually inactive at the human VR1 (EC50>10 μM). Capsazepine and ruthenium red were both more potent at blocking the capsaicin response of human VR1 than rat VR1. Capsazepine blocked the human but not the rat VR1 response to low pH. Capsazepine was also more effective at inhibiting the noxious heat response of human than of rat VR1. British Journal of Pharmacology (2001) 132, 1084–1094; doi:10.1038/sj.bjp.0703918