Endocannabinoid turnover in GtoPdb v.2021.3

IUPHAR/BPS Guide to Pharmacology CITE, vol. 2021

Abstract

The principle endocannabinoids are 2-acylglycerol esters, such as 2-arachidonoylglycerol (2-AG), and N-acylethanolamines, such as anandamide (N-arachidonoylethanolamine, AEA). The glycerol esters and ethanolamides are synthesised and hydrolysed by parallel, independent pathways. Mechanisms for release and re-uptake of endocannabinoids are unclear, although potent and selective inhibitors of facilitated diffusion of endocannabinoids across cell membranes have been developed [28]. FABP5 (Q01469) has been suggested to act as a canonical intracellular endocannabinoid transporter in vivo [17]. For the generation of 2-arachidonoylglycerol, the key enzyme involved is diacylglycerol lipase (DAGL), whilst several routes for anandamide synthesis have been described, the best characterized of which involves N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD, [70]). A transacylation enzyme which forms N-acylphosphatidylethanolamines has been identified as a cytosolic enzyme, PLA2G4E (Q3MJ16) [62]. In vitro experiments indicate that the endocannabinoids are also substrates for oxidative metabolism via cyclooxygenase, lipoxygenase and cytochrome P450 enzyme activities [5, 23, 72].

Authors 5

1. S P H Alexander

   University of Nottingham

   Affiliation as printed

   University of Nottingham

2. Patrick Doherty

   King's College London

   Affiliation as printed

   King's College London

3. Christopher John Fowler

   University Hospital of Umeå

   Affiliation as printed

   University Hospital of Umeå

4. Jürg Gertsch

   University of Bern

   Affiliation as printed

   University of Bern

5. Mario van der Stelt Aachen

   Leiden University

   Affiliation as printed

   Leiden University