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The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1)
Author(s) -
Smart D,
Gunthorpe M J,
Jerman J C,
Nasir S,
Gray J,
Muir A I,
Chambers J K,
Randall A D,
Davis J B
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703050
Subject(s) - anandamide , capsazepine , endocannabinoid system , chemistry , cannabinoid , cannabinoid receptor , trpv1 , agonist , pharmacology , capsaicin , receptor , transient receptor potential channel , biochemistry , medicine
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