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Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in

By Aron H. Lichtman, E. Gregory Hawkins, Graeme Griffin and Benjamin F. Cravatt

Abstract

Fatty acid amides (FAAs) represent a class of neuromodulatory lipids that includes the endocannabinoid anandamide and the sleep-inducing substance oleamide. Both anandamide and oleamide produce behavioral effects indicative of cannabinoid activity, but only anandamide binds the cannabinoid (CB1) receptor in vitro. Accordingly, oleamide has been proposed to induce its behavioral effects by serving as a competitive substrate for the brain enzyme fatty acid amide hydrolase (FAAH) and inhibiting the degradation of endogenous anandamide. To test the role that FAAH plays as a mediator of oleamide activity in vivo, we have compared the behavioral effects of this FAA in FAAH(�/�) and (�/�) mice. In both genotypes, oleamide produced hypomotility, hypothermia, and ptosis, all of which were enhanced in FAAH(�/�) mice, were unaffected by the CB

Year: 2002
OAI identifier: oai:CiteSeerX.psu:10.1.1.322.1429
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