Activated cardiac adenosine A1 receptors translocate out of caveolae

Abstract

The cardiac affects of the purine nucleoside, adenosine, are well known. Adenosine 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 vicinity of the plasma membrane. Several reports demonstrate that G protein-coupled receptors redistribute to caveolae in response to receptor occupation. In this study, we tested the hypothesis that adenosine A1 receptors would translocate to caveolae in the presence of agonists. Surprisingly, in unstimulated rat cardiac ventricular myocytes, 67 ± 5% of adenosine A1 receptors were isolated with caveolae. However, incubation with the adenosine A1 receptor agonist 2-chlorocyclopentyladenosine induced the rapid translocation of the A1 receptors from caveolae into non-caveolae plasma membrane, an effect that was blocked by the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. An adenosine A(2A) receptor agonist did not alter the localization of A1 receptors to caveolae. These data suggest that the translocation of A1 receptors out of caveolae and away from compartmentalized signaling molecules may explain why activation of ventricular myocyte A1 receptors are associated with few direct effects.