Linked Life Data

9918562

Source:http://linkedlifedata.com/resource/pubmed/id/9918562

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pubmed-article:9918562pubmed:abstractTextIn the present report, we investigated in detail the effects of SR 144528, a selective antagonist of the peripheral cannabinoid receptor (CB2), on two well-characterized functions mediated by CB2: the induction of the early response gene krox24 and the inhibition of adenylyl cyclase. We generated Chinese hamster ovary cells doubly transfected with human CB2 and a luciferase reporter gene linked to either the murine krox24 regulatory sequence or multiple cAMP responsive elements. Our results show that (1) SR 144528 antagonizes the effect of receptor agonists-it inhibits the krox24 reporter activity and prevents the inhibition of forskolin-induced cAMP reporter activity mediated by CP 55,940; (2) CB2 is autoactivated-CB2 mediates signaling in the absence of ligand, and this basal activity is reduced by pretreating the cells with pertussis toxin; (3) SR 144528 is an inverse agonist-it reproduces the effects of pertussis toxin; and (4) inhibition of precoupled CB2 by a long-term pretreatment of cells with SR 144528 potentiates krox24 response to cannabinoid receptor agonists and restores activation of adenylyl cyclase. Taken together, these data provide evidences for the inverse agonist property of SR 144528 and the constitutive activation of CB2 in Chinese hamster ovary-expressing cells.lld:pubmed
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pubmed-article:9918562pubmed:articleTitleSR 144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist.lld:pubmed
pubmed-article:9918562pubmed:affiliationSanofi Recherche, Montpellier Cedex, France. marielle.portier@tls1.elsanofi.frlld:pubmed
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