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The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects.

The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Research Abstract Details 

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  • The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Abstract Text:

    d g johnsD G Johns,d j behmD J Behm,d j walkerD J Walker,z aoZ Ao,e m shaplandE M Shapland,d a danielsD A Daniels,m riddickM Riddick,s dowellS Dowell,p c statonP C Staton,p greenP Green,u shabonU Shabon,w baoW Bao,n aiyarN Aiyar,t-l yueT-L Yue,a j brownA J Brown,a d morrisonA D Morrison,s a douglasS A Douglas,

    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 GTPgammaS 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 GTPgammaS activity (EC50 approximately 2 nM), whereas the CB1 and CB2-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 (IC50 approximately 3 micro 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.

    The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Publishing Authors By Initials

    dg johnsDG Johns,dj behmDJ Behm,dj walkerDJ Walker,z aoZ Ao,em shaplandEM Shapland,da danielsDA Daniels,m riddickM Riddick,s dowellS Dowell,pc statonPC Staton,p greenP Green,u shabonU Shabon,w baoW Bao,n aiyarN Aiyar,tl yueTL Yue,aj brownAJ Brown,ad morrisonAD Morrison,sa douglasSA Douglas,

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    The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: British journal of pharmacology

    VOLUME: 152

    Page Numbers: 825-31

    Journal Abbreviation: Br. J. Pharmacol.

    ISSN: 0007-1188

    DAY: 20

    MONTH: 08

    YEAR: 2007

    The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Information

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    LANGUAGE: eng

    NlmUniqueID: 7502536

    The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Keywords Mesh Terms:

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    Grant and Affiliation Information for The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects.

    AFFILIATION: GlaxoSmithKline, Cardiovascular and Urogenital Center for Excellence in Drug Discovery, Vascular Biology and Thrombosis, King of Prussia, PA 19406, USA. Douglas.G.Johns@gsk.com

    Country: England

    England Research PublicationEngland Research Publication

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    MEDLINETA: Br J Pharmacol

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