School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Curr Top Med Chem. 2010;10(8):828-58. doi: 10.2174/156802610791164238.
Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are hydrolytic enzymes which degrade the endogenous cannabinoids (endocannabinoids) N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), respectively. Endocannabinoids are an important class of lipid messenger molecules that are produced on demand in response to elevated intracellular calcium levels. They recognize and activate the cannabinoid CB(1) and CB(2) receptors, the molecular targets for Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in marijuana evoking several beneficial therapeutic effects. However, in vivo the cannabimimetic effects of AEA and 2-AG remain weak owing to their rapid inactivation by FAAH and MGL, respectively. The inactivation of FAAH and MGL by specific enzyme inhibitors increases the levels of AEA and 2-AG, respectively, producing therapeutic effects such as pain relief and depression of anxiety.
脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MGL）是水解酶，分别降解内源性大麻素（大麻素）N-花生四烯酰乙醇胺（花生四烯酸乙醇胺，AEA）和 2-花生四烯酰甘油（2-AG）。内源性大麻素是一类重要的脂质信使分子，它们是在细胞内钙离子水平升高时按需产生的。它们识别并激活大麻素 CB1 和 CB2 受体，这是大麻中 Delta(9)-四氢大麻酚（Delta(9)-THC）的分子靶点，引发多种有益的治疗效果。然而，在体内，AEA 和 2-AG 的大麻样作用仍然较弱，这是由于它们分别被 FAAH 和 MGL 快速灭活。特异性酶抑制剂对 FAAH 和 MGL 的失活分别增加了 AEA 和 2-AG 的水平，产生了治疗效果，如缓解疼痛和抑制焦虑。
