Endocannabinoid turnover

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The principle endocannabinoids are 2-arachidonoylglycerol (2AG) and anandamide (N-arachidonoylethanolamine, AEA), thought to be generated on demand rather than stored, although this may not always be the case [4]. Mechanisms for release and re-uptake of endocannabinoids (and related entities) are unclear, although candidates for intracellular transport have been suggested. For the generation of 2-arachidonoylglycerol, the key enzyme involved is diacylglycerol lipase (DGL), whilst several routes for anandamide synthesis have been described, the best characterized of which involves N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD, [18]). Inactivation of these endocannabinoids appears to occur predominantly through monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) for 2-arachidonoylglycerol and anandamide, respectively. Note that these enzymes also contribute to the turnover of many endogenous ligands inactive at CB1 and CB2 cannabinoid receptors, such as N-oleoylethanolamide, N-palmitoylethanolamine and 2-oleoyl glycerol. In vitro experiments indicate that the endocannabinoids are also substrates for oxidative metabolism via cyclooxygenase, lipoxygenase and cytochrome P450 enzyme activities [3,7,19].

Enzymes

DGLα (Diacylglycerol lipase α) Show summary » More detailed page

DGLβ (Diacylglycerol lipase β) Show summary » More detailed page

MGL (Monoacylglycerol lipase) Show summary » More detailed page

FAAH (Fatty acid amide hydrolase) Show summary » More detailed page

NAPE-PLD (N-Acylphosphatidylethanolamine-phospholipase D) Show summary »

FAAH2 (Fatty acid amide hydrolase-2) Show summary » More detailed page

NAAA (N-Acylethanolamine acid amidase) Show summary » More detailed page

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Christopher Fowler. Endocannabinoid turnover. Accessed on 23/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=273.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.