title: Activated cardiac adenosine A(1) 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 A(1) receptors would translocate to caveolae in the presence of agonists. Surprisingly, in unstimulated rat cardiac ventricular myocytes, 67 +/- 5% of adenosine A(1) receptors were isolated with caveolae. However, incubation with the adenosine A(1) receptor agonist 2-chlorocyclopentyladenosine induced the rapid translocation of the A(1) receptors from caveolae into non-caveolae plasma membrane, an effect that was blocked by the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. An adenosine A(2a) receptor agonist did not 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 compartmentalized signaling molecules may explain why activation of ventricular myocyte A(1) receptors are associated with few direct effects.
authors.affiliation: Department of Surgery, University of Kentucky Medical School, Lexington, Kentucky 40536, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Lasley
authors.forename: P
authors.initials: P
authors.lastname: Narayan
authors.forename: A
authors.initials: A
authors.lastname: Uittenbogaard
authors.forename: E J
authors.initials: EJ
authors.lastname: Smart
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D051244:Caveolin 3; D022461:Caveolins; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C495549:Cav3 protein, rat; D051244:Caveolin 3; D022461:Caveolins; D008565:Membrane Proteins; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C058394:2-chloro-N(6)cyclopentyladenosine; D002784:Cholesterol; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D000241:Adenosine