alpha(2A)-adrenoceptor: G(alphai1) protein-mediated pertussis toxin-resistant attenuation of G(s) coupling to the cyclic AMP pathway.
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Rauly I, Ailhaud M, Wurch T, Pauwels PJ
alpha(2A)-adrenoceptor: G(alphai1) protein-mediated pertussis toxin-resistant attenuation of G(s) coupling to the cyclic AMP pathway.
Biochem Pharmacol. 2000 Jun 15;59(12):1531-8.
- PubMed ID
- 10799649 [ View in PubMed]
- Abstract
Fusion proteins were constructed between a recombinant human alpha(2A)-adrenoceptor and either a rat wild-type G(alphai1) or putative pertussis toxin-resistant form of the G(alphai1) protein (G(alphai1)Cys(351)Gly). [(3)H]2-[2-(2-Methoxy-1, 4-benzodioxanyl)]imidazoline hydrochloride (RX 821002) saturation binding experiments demonstrated that both fusion proteins were expressed at a similar level as the alpha(2A)-adrenoceptor co-expressed with either a wild-type G(alphai1) or mutant G(alphai1)Cys(351)Gly protein in COS-7 cells, and displayed a ligand binding profile similar to that for the alpha(2A)-adrenoceptor protein. In alpha(2A)-adrenoceptor-transfected COS-7 cells, 5-bromo-6-(2-imidazolin-2-yl-amino) quinoxaline tartrate (brimonidine, 10 microM) induced stimulation (151 +/- 28%) of adenosine 3',5'-cyclic monophosphate (cAMP) formation which was prevented by cholera toxin treatment, demonstrating a direct coupling of the alpha(2A)-adrenoceptor to an endogenous G(alphas) protein in COS-7 cells. Expression of either the wild-type G(alphai1) or mutant G(alphai1)Cys(351)Gly protein in co-expression or fusion with the alpha(2A)-adrenoceptor in COS-7 cells suppressed the brimonidine-induced stimulation of cAMP formation, both in the presence and absence of pertussis toxin pretreatment. Hence, the G(alphai1) protein apparently blocks the G(s)-coupled alpha(2A)-adrenoceptor-mediated pathway in a pertussis toxin-non-sensitive way.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Brimonidine Alpha-2A adrenergic receptor Protein Humans YesAgonistDetails