Effects of a commonly occurring genetic polymorphism of human CYP3A4 (I118V) on the metabolism of anandamide.

ABSTRACT: The endocannabinoid system plays an important role in numerous physiological processes including mood, appetite, and pain sensation. A critical compound in maintaining cannabinoid tone is the endocannabinoid anandamide (AEA). We have recently shown that AEA is metabolized by several different human cytochromes P450 (P450) to form a number of metabolites, one of which exhibits increased biological activity. CYP3A4, one of the major P450s involved in the metabolism of AEA, produces four major metabolites. One of these metabolites, 5,6-epoxyeicosatrienoic acid ethanolamide (5,6-EET-EA), exhibits a much higher affinity than AEA for the cannabinoid 2 receptor (CB-2), which leads to a marked decrease in intracellular cAMP levels in cells expressing CB-2. There are multiple human alleles of CYP3A

SUBMITTER: Pratt-Hyatt M 

PROVIDER: S-EPMC2967395 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature