2-Arachidonoylglycerol (2-AG) is a component of the endocannabinoid receptor pathway and is primarily hydrolyzed by monoacylglycerol lipase (MAGL) in vivo. We found that the non-specific serine esterase, butyrylcholinesterase (BChE), can hydrolyze 2-AG with reasonable affinity and may present a new compensatory mechanism for endocannabinoid regulation. In vitro hydrolysis reactions of 2-AG with equine BChE were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) positive/negative electrospray ionization (ESI+/-) to measure the formation of arachidonic acid (AA) and the loss of 2-AG over time (min). The resulting Michaelis-Menten approximations reveal that BChE has affinity towards 2-AG in phosphate buffer at neutral pH (7.4). The calculated V_max, K_m and k_cat were 12.1 nmol s^-1, 57.5 μM, and 0.073 s^-1, respectively, which produced a diffusion-controlled rate of association (k_cat/K_m) of 1.3 x 10³ M^-1 s^-1. Human BChE 2-AG hydrolysis was measured by immunoprecipitating BChE from fresh plasma and monitoring 2-AG loss and AA formation over time. These findings show that BChE can hydrolyze 2-AG and which may be evidence of a more specific role for BChE in endocannabinoid regulation.
Copyright © 2013. Published by Elsevier Inc.

PMID:

 23689009
[PubMed – as supplied by publisher]                                                                                http://www.ncbi.nlm.nih.gov/pubmed/23689009