Brain monoglyceride lipase participating in endocannabinoid inactivation

• DOI: 10.1073/pnas.152334899
• Publication Date: 2002-09-30T16:42:53Z
• Authors: T. P. Dinh; D. Carpenter; F. M. Leslie; T. F. Freund; I. Katona; S. L. Sensi; S. Kathuria; D. Piomelli
• Keywords: 2-Arachidonoylglycerol; Diacylglycerol lipase

The endogenous cannabinoids (endocannabinoids) are lipid molecules that may mediate retrograde signaling at central synapses and other forms of short-range neuronal communication. monoglyceride 2-arachidonoylglycerol (2-AG) meets several criteria an endocannabinoid substance: ( i ) it activates cannabinoid receptors; ii is produced by neurons in activity-dependent manner; iii rapidly eliminated. 2-AG inactivation only partially understood, but occur transport into cells enzymatic hydrolysis. Here we tested the hypothesis lipase (MGL), a serine hydrolase converts monoglycerides to fatty acid glycerol, participates inactivation. We cloned MGL homology from rat brain cDNA library. Its sequence encoded for 303-aa protein with calculated molecular weight 33,367 daltons. Northern blot situ hybridization analyses revealed mRNA heterogeneously expressed brain, highest levels regions where CB 1 receptors also present (hippocampus, cortex, anterior thalamus, cerebellum). Immunohistochemical studies hippocampus showed distribution has striking laminar specificity, suggesting presynaptic localization enzyme. Adenovirus-mediated transfer cortical increased expression attenuated N -methyl-D-aspartate/carbachol-induced accumulation these cells. No such effect was observed on anandamide, another lipid. results suggest hydrolysis means primary mechanism intact neurons.