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

1 Vaniiloid receptors (VR1) were cloned from human and rat dorsal root gang lion libraries and expressed in Xenopus oocytes or Chinese Hamster Ovary (C HO) cells. 2 Both rat and human VR1 formed ligand gated channels that were activated b y 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 muM; human = 1.90+/-0.30 muM: CHO cells: rat = 0.20+/-0.06 muM; human = 0.19+/-0.08 muM). 3 In CHO cell lines co-expressing either rat or human VR1 and the calcium s ensitive, luminescent protein. aequorin, the EC50 values for capsaicin-indu ced responses were similar in both cell lines (rat = 0.35+/-0.06 muM, human = 0.53+/-0.03 muM). 4 The threshold for activation by acidic solutions was lower for human VRI channels than that for rat VRI (EC50 pH 5.49+/-0.04 and pH 5.7+/-0.09, resp ectively). 5 The threshold for heat activation was identical (42 degreesC) for rat and human VRI. 6 PPAHV was an agonist at rat VR1 (EC50 between 3 and 10 muM) but was virtu ally inactive at the human VR1 (EC50>10 muM). 7 Capsazepine and ruthenium red were both more potent at blocking the capsa icin response of human VR1 than rat VRI. 8 Capsazepine blocked the human but not the rat VRI response to low pH. Cap sazepine was also more effective at inhibiting the noxious heat response of human than of rat VR1.