SR 144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist.

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47

摘要:

In the present report, we investigated in detail the effects of SR 144528, a selective of the peripheral cannabinoid receptor (), on two well-characterized functions mediated by : the induction of the early response gene and the inhibition of . We generated ovary cells doubly transfected with and a reporter gene linked to either the regulatory sequence or multiple cAMP responsive elements. Our results show that (1) SR 144528 antagonizes the effect of receptor -it inhibits the reporter activity and prevents the inhibition of -induced cAMP reporter activity mediated by CP 55,940; (2) is autoactivated-mediates signaling in the absence of ligand, and this basal activity is reduced by pretreating the cells with toxin; (3) SR 144528 is an inverse -it reproduces the effects of toxin; and (4) inhibition of precoupled by a long-term pretreatment of cells with SR 144528 potentiates response to cannabinoid receptor and restores activation of . Taken together, these data provide evidences for the inverse property of SR 144528 and the constitutive activation of in ovary-expressing cells.

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DOI:

10.1016/S0022-3565(24)37993-5

被引量:

252

年份:

1999

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2010
被引量:29

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