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Good news for CB 1 receptors: endogenous agonists are in the right place
Author(s) -
Maccarrone M
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707566
Subject(s) - endocannabinoid system , anandamide , cannabinoid receptor , caveolae , 2 arachidonoylglycerol , receptor , microbiology and biotechnology , paracrine signalling , g protein coupled receptor , depolarization induced suppression of inhibition , autocrine signalling , cannabinoid , lipid raft , gpr18 , endogeny , chemistry , cannabinoid receptor type 2 , biology , neuroscience , biochemistry , signal transduction , agonist
Endocannabinoids are endogenous ligands of brain‐type (CB 1 ) and spleen‐type (CB 2 ) cannabinoid receptors. N ‐Arachidonoylethanolamine (anandamide, AEA) and 2‐arachidonoylglycerol (2‐AG) are prototype members of the fatty acid amides and the monoacylglycerols, two groups of endocannabinoids. Unlike CB 1 , CB 2 receptors do not reside within ‘caveolae’, specialized membrane microdomains that are well‐known modulators of the activity of a number of G protein‐coupled receptors. In this issue of the British Journal of Pharmacology , Rimmerman and coworkers demonstrate that 2‐AG is entirely localized in the caveolae of dorsal root ganglion cells, where also part of AEA (∼30%) can be detected. However, most of AEA (∼70%) was detected in non‐caveolae fractions, that is where CB 2 receptors are localized. The different interaction of AEA and 2‐AG with membrane microdomains might have significant implications for endocannabinoid‐dependent autocrine and/or retrograde‐paracrine signalling pathways. It also raises an important question about the structural determinants responsible for a different localization of two apparently similar endocannabinoids within lipid bilayers. British Journal of Pharmacology (2008) 153 , 179–181; doi: 10.1038/sj.bjp.0707566 ; published online 12 November 2007