Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6
. Proc Natl Acad Sci U S A 2013; 110: 17558-63.
(91) ABHD6 acts as lysophospholipase or monoacylglycerol lipase, the latter being possibly related to the regulation of 2-arachidonoyl glycerol (2-AG) signaling.
(2010) The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors.
The facilitatory effect of mGluR5 activation on mPFC output was restored with inhibitors of the postsynaptic 2-AG hydrolyzing enzyme ABHD6
(intracellular WWL70) and the monoacylglycerol lipase MGL (JZL184) to increase availability of 2-AG in the postsynaptic cell or with a [GABA.sub.A] receptor blocker (intracellular picrotoxin) .
Importantly, the research team discovered that an enzyme called alpha/beta hydrolase domain-6 (in short ABHD6) breaks down monoacylglycerol and thus negatively controls insulin release.
These researchers said that "an ideal drug for type-2 diabetes would increase insulin levels in blood by enhancing the beta cells response to glucose only when it is elevated and also increase the sensitivity of body tissues to insulin; this is precisely what ABHD6 inhibition does and thus we have identified a unique new target for type 2 diabetes."
(36)) A functional proteomic study has demonstrated that MGL accounts for ~85% of 2-AG hydrolysis, and that other enzymes, such as [alpha]/[beta] hydrolase domain 6 and 12 (ABHD6 and ABHD12), contributes to the hydrolysis of the remaining 15%.
Postsynaptic COX-2 and ABHD6 may also contributes to inactivation of 2-AG.