Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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 microM) and capsaicin (1 microM) produced similar inward currents in hVR1 transfected, but not in parental, HEK293 cells. These currents were abolished by capsazepine (1 microM). 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 (pK(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.

Original publication

DOI

10.1038/sj.bjp.0703050

Type

Journal article

Journal

Br J Pharmacol

Publication Date

01/2000

Volume

129

Pages

227 - 230

Keywords

Amides, Arachidonic Acids, Binding, Competitive, Calcium, Calcium Channels, Cannabinoids, Capsaicin, Cell Line, Cloning, Molecular, Electrophysiology, Endocannabinoids, Ethanolamines, Humans, Hydrogen-Ion Concentration, Palmitic Acids, Patch-Clamp Techniques, Polyunsaturated Alkamides, Receptors, Drug, Recombinant Proteins, TRPV Cation Channels