D Smart1, Martin J. Gunthorpe1, Jeffrey C. Jerman1, S. Nasir1, Julie Gray1, Aaron Muir2, Jon Chambers2, Andrew D. Randall1, Janet L. Davis1
1Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, U.K.
2Vascular Biology, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, U.K.
Tóm tắt
The endogenous cannabinoid anandamide was identified as an agonist for the recombinant human VR1 (hVR1) by screening a large array of bioactive substances using a FLIPR‐based calcium assay. Further electrophysiological studies showed that anandamide (10 or 100 μM) and capsaicin (1 μM) produced similar inward currents in hVR1 transfected, but not in parental, HEK293 cells. These currents were abolished by capsazepine (1 μM). In the FLIPR anandamide and capsaicin were full agonists at hVR1, with pEC50 values of 5.94±0.06 (n=5) and 7.13±0.11 (n=8) respectively. The response to anandamide was inhibited by capsazepine (pKB of 7.40±0.02, n=6), but not by the cannabinoid receptor antagonists AM630 or AM281. Furthermore, pretreatment with capsaicin desensitized the anandamide‐induced calcium response and vice versa. In conclusion, this study has demonstrated for the first time that anandamide acts as a full agonist at the human VR1.British Journal of Pharmacology (2000) 129, 227–230; doi:10.1038/sj.bjp.0703050
