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

TLDR

Anandamide was identified as an agonist for the recombinant human VR1 (hVR1) through a FLIPR‑based calcium assay screening of many bioactive compounds. Anandamide and capsaicin produce comparable full agonist currents in hVR1‑transfected HEK293 cells, both blocked by capsazepine but not by cannabinoid antagonists, and cross‑desensitization between the two ligands confirms anandamide as a full agonist at hVR1. Published in British Journal of Pharmacology, 2000, 129:227–230 (doi:10.1038/sj.bjp.0703050).

Abstract

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 μ M ) and capsaicin (1 μ M ) produced similar inward currents in hVR1 transfected, but not in parental, HEK293 cells. These currents were abolished by capsazepine (1 μ M ). In the FLIPR anandamide 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 (p K B 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