Activated cardiac adenosine A(1) receptors translocate out of caveolae

The cardiac affects of the purine nucleoside, adenosine, are well known. Ad enosine increases coronary blood flow, exerts direct negative chronotropic and dromotropic effects, and exerts indirect anti-adrenergic effects. These effects of adenosine are mediated via the activation of specific G protein -coupled receptors, There is increasing evidence that caveolae play a role in the compartmentalization of receptors and second messengers in the vicin ity of the plasma membrane. Several reports demonstrate that G protein-coup led receptors redistribute to caveolae in response to receptor occupation. In this study, we tested the hypothesis that adenosine A(1) receptors would translocate to caveolae in the presence of agonists, Surprisingly, in unst imulated rat cardiac ventricular myocytes, 67 +/- 5% of adenosine A(1) rece ptors were isolated with caveolae. However, incubation with the adenosine A (1) receptor agonist 2-chlorocyclopentyladenosine induced the rapid translo cation of the A(1) receptors from caveolae into non-caveolae plasma membran e, an effect that was blocked by the adenosine A(1) receptor antagonist, 8- cyclopentyl-1,3-dipropylxanthine. An adenosine A(2a) receptor agonist did n ot alter the localization of A(1) receptors to caveolae, These data suggest that the translocation of A(1) receptors out of caveolae and away from com partmentalized signaling molecules may explain why activation of ventricula r myocyte A(1) receptors are associated with few direct effects.