Anandamide amidohydrolase reacting with 2‐arachidonoylglycerol, another cannabinoid receptor ligand

FEBS Letters

Goparaju, Sravan Kumar¹  Yamamoto, Shozo¹  Ueda, Natsuo¹  Yamaguchi, Hiroko¹ 

[1] Department of Biochemistry, Tokushima University, School of Medicine, Kuramoto-cho, Tokushima 770, Japan

关键词: Cannabinoid;    Anandamide;    2-Arachidonoylglycerol;    Amidohydrolase;    COS-7 cell;   

DOI  :  10.1016/S0014-5793(97)01603-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Two endogenous ligands for cannabinoid receptors, anandamide (arachidonylethanolamide) and 2-arachidonoylglycerol, lose their biological activities by enzymatic hydrolysis. A cDNA for a rat liver enzyme hydrolyzing anandamide as well as oleamide was overexpressed in COS-7 cells. When the particulate fraction was allowed to react with 2-arachidonoylglycerol, arachidonic acid was produced. In contrast, this hydrolytic reaction did not occur with the control cells. The hydrolysis of 2-arachidonoylglycerol proceeded about 4-fold faster than the anandamide hydrolysis with a K _m value as low as 6 μM and an optimal pH of 10. Phenylmethylsulfonyl fluoride and methyl arachidonyl fluorophosphonate inhibited the hydrolysis of both anandamide and 2-arachidonoylglycerol in parallel. Furthermore, the hydrolysis of [¹⁴C]2-arachidonoylglycerol was inhibited by anandamide dose-dependently. These results suggest that anandamide and 2-arachidonoylglycerol can be inactivated by the same enzyme.

【 授权许可】

Unknown