Review

Subject Category: Review Article

British Journal of Pharmacology (2007) 152, 602–623; doi:10.1038/sj.bjp.0707456; published online 17 September 2007

The complications of promiscuity: endocannabinoid action and metabolism

S P H Alexander1 and D A Kendall1

1School of Biomedical Sciences and Institute of Neuroscience, University of Nottingham Medical School, Nottingham NG7 7LP, UK

Correspondence: Dr SPH Alexander, School of Biomedical Sciences and Institute of Neuroscience, University of Nottingham Medical School, Nottingham NG7 2UH, UK. E-mail: steve.alexander@nottingham.ac.uk

Received 18 July 2007; Revised 15 August 2007; Accepted 16 August 2007; Published online 17 September 2007.

Top

Abstract

In this review, we present our understanding of the action and metabolism of endocannabinoids and related endogenous molecules. It is clear that the interactions between the multiple endocannabinoid-like molecules (ECLs) are highly complex, both at the level of signal transduction and metabolism. Thus, ECLs are a group of ligands active at 7-transmembrane and nuclear receptors, as well as transmitter-gated and ion channels. ECLs and their metabolites can converge on common endpoints (either metabolic or signalling) through contradictory or reinforcing pathways. We highlight the complexity of the endocannabinoid system, based on the promiscuous nature of ECLs and their metabolites, as well as the synthetic modulators of the endocannabinoid system.

Keywords:

cannabinoid receptors, endocannabinoid metabolism, TRPV1 vanilloid receptors, peroxisome proliferator-activated receptors

Abbreviations:

2AG, 2-arachidonoylglycerol; AEA, anandamide (N-arachidonoylethanolamine); AM404, N-(4-hydroxyphenyl)-5z,8z,11z,14z-eicosatetraenamide; ABC, ATP-binding cassette; CNS, central nervous system; CYP450, cytochrome P450; ECL, endocannabinoid-like molecules; ERK, extracellular signal-regulated kinase; FAAH, fatty acid amide hydrolase; GIRK, G protein-coupled inwardly rectifying potassium; GRK, G-protein-coupled receptor kinase; JNK, c-Jun N-terminal kinase; LOX, lipoxygenases; LY2183240, 5-biphenyl-4-ylmethyl-tetrazole-1-carboxylic acid dimethylamide; MAGL, monoacylglycerol lipase; MAP kinase, mitogen-activated protein kinase; NADA, N-arachidonoyldopamine; NAGly, N-arachidonoylglycine; NAPE, N-acylphosphatidylethanolamine; NAT, N-arachidonoyltaurine; ODA, oleamide (octadec(9,10z)enamide); OEA, N-oleoylethanolamine; PEA, N-palmitoylethanolamine; PLC, phospholipase C; PPAR, peroxisome proliferator-activated receptor; 7TM, 7-transmembrane; TRP, transient receptor potential; UCM707, N-(3-furanylmethyl)-5z,8z,11z,14z-eicosatetraenamide; URB597, cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester; VDM11, N-(4-hydroxy-2-methylphenyl)-5z,8z,11z,14z-eicosatetraenamides

Top

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated

NEWS AND VIEWS

Why endocannabinoids are not all alike

Nature Neuroscience News and Views (01 Feb 2008)

Extra navigation

.

naturejobs

natureproducts


ADVERTISEMENT