Anandamide and the vanilloid receptor (TRPV1).

Arachidonylethanolamide (anandamide) was identified some 15 years ago as a brain constituent that binds to the cannabinoid receptor. After this seminal discovery, multiple new receptors for anandamide have been identified, including the vanilloid receptor (TRPV1), and anandamide is now frequently referred as an "endovanilloid." Characterization of the action of anandamide on TRPV1 revealed that (1) the potency and efficacy of anandamide on TRPV1 very much depend on the species and tissue, (2) anandamide responsiveness in vivo is significantly controlled by its local metabolism, (3) anandamide activation of cannabinoid receptors regulates TRPV1 responsiveness, (4) TRPV1 activation regulates anandamide synthesis, (5) anandamide metabolites affect TRPV1 responses, (6) the often observed convergent physiological actions of anandamide and TRPV1 agonists in neither case necessarily represent direct effects on TRPV1, and (7) coactivation of the cannabinoid receptors and TRPV1 often complicates the distinction between these pathways. These issues are reviewed here together with the potential implications for the pathophysiological and pharmacological regulation of inflammatory, respiratory, and cardiovascular disorders, as well as of appetite and fat metabolism.