Enzymes of porcine brain hydrolyzing 2-arachidonoylglycerol, an endogenousligand of cannabinoid receptors

Anandamide and 2-arachidonoylglycerol (2-AG) are two endogenous ligands for the cannabinoid receptors, and their cannabimimetic activities are lost wh en they are hydrolyzed enzymatically. Cytosol and particulate fractions of porcine brain exhibited a high 2-AG hydrolyzing activity of 100 nmol/min/mg protein. Most of the activity could be attributed to a monoacylglycerol li pase-like enzyme that did not hydrolyze anandamide. It was separated by hyd roxyapatite chromatography from anandamide amidohydrolase, which is also ca pable of hydrolyzing 2-AG as well as anandamide. Thus, porcine brain has at least two enzymes capable of hydrolyzing 2-AG. The 2-AG hydrolase activiti es of both the cytosolic and particulate enzymes were irreversibly and time -dependently inhibited by methyl arachidonyl fluorophosphonate with IC50 va lues as low as 2-3 nM. (C) 1999 Elsevier Science Inc.