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.
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
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)
RESEARCH
Endocannabinoids in Chronic Migraine: CSF Findings Suggest a System Failure
Neuropsychopharmacology Original Article


