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The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects
Author(s) -
Johns D G,
Behm D J,
Walker D J,
Ao Z,
Shapland E M,
Daniels D A,
Riddick M,
Dowell S,
Staton P C,
Green P,
Shabon U,
Bao W,
Aiyar N,
Yue TL,
Brown A J,
Morrison A D,
Douglas S A
Publication year - 2007
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.0707419
Subject(s) - cannabinoid receptor , cannabidiol , pharmacology , endocannabinoid system , cannabinoid receptor type 2 , vasodilation , cannabinoid , agonist , cannabinoid receptor antagonist , chemistry , medicine , receptor , cannabis , psychiatry
Background and purpose: Atypical cannabinoids are thought to cause vasodilatation through an as‐yet unidentified ‘CBx’ receptor. Recent reports suggest GPR55 is an atypical cannabinoid receptor, making it a candidate for the vasodilator ‘CBx’ receptor. The purpose of the present study was to test the hypothesis that human recombinant GPR55 is activated by atypical cannabinoids and mediates vasodilator responses to these agents. Experimental approach: Human recombinant GPR55 was expressed in HEK293T cells and specific GTP γ S activity was monitored as an index of receptor activation. In GPR55‐deficient and wild‐type littermate control mice, in vivo blood pressure measurement and isolated resistance artery myography were used to determine GPR55 dependence of atypical cannabinoid‐induced haemodynamic and vasodilator responses. Key results: Atypical cannabinoids O‐1602 and abnormal cannabidiol both stimulated GPR55‐dependent GTP γ S activity (EC 50 approximately 2 n M ), whereas the CB 1 and CB 2 ‐selective agonist WIN 55,212‐2 showed no effect in GPR55‐expressing HEK293T cell membranes. Baseline mean arterial pressure and heart rate were not different between WT and GPR55 KO mice. The blood pressure‐lowering response to abnormal cannabidiol was not different between WT and KO mice (WT 20±2%, KO 26±5% change from baseline), nor was the vasodilator response to abnormal cannabidiol in isolated mesenteric arteries (IC 50 approximately 3 μ M for WT and KO). The abnormal cannabidiol vasodilator response was antagonized equivalently by O‐1918 in both strains. Conclusions: These results demonstrate that while GPR55 is activated by atypical cannabinoids, it does not appear to mediate the vasodilator effects of these agents. British Journal of Pharmacology (2007) 152 , 825–831; doi: 10.1038/sj.bjp.0707419 ; published online 20 August 2007