The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1)

The endogenous cannabinoid anandamide was identified as an agonist for the recombinant human VRI (hVR1) by screening a large array of bioactive substa nces using a FLIPR-based calcium assay. Further electrophysiological studie s showed that anandamide (10 or 100 mu M) and capsaicin (1 mu M) produced s imilar inward currents in hVR1 transfected, but not in parental, HEK293 cel ls. These currents were abolished by capsazepine (1 mu M). In the FLIPR ana ndamide and capsaicin were full agonists at hVR1, with pEC(50) values of 5. 94 +/- 0.06 (n = 5) and 7.13 +/- 0.11 (n = 8) respectively. The response to anandamide was inhibited by capsazepine (pK(B) of 7.40 +/- 0.02, n = 6), b ut not by the cannabinoid receptor antagonists AM630 or AM281. Furthermore, pretreatment with capsaicin desensitized the anandamide-induced calcium re sponse and vice versa. In conclusion, this study has demonstrated for the f irst time that anandamide acts as a full agonist at the human VR1.