title: Adenosine 3',5'-monophosphate, the myocardial cell membrane, and calcium.
abstract: Catecholamine-sensitive adenylate cyclase, cyclic nucleotide phosphodiesterase, adenosine 3', 5'-monophosphate (cyclic AMP)-dependent protein kinase, kinase substrate, and phosphoprotein phosphatase have variously been reported to be present in preparations of myocardial cellular membranes that function in the movement of Ca2+ in and out of the cell and in intracellular Ca2+ translocations, indicating that these membranees possess the equipment for the formation and destruction of cyclic Amp as well as for the initiation, effectuation, and termination of a possible membrane action of the nucleotide. It has also been observed that phosphorylation of seryl residues of protein in sarcolemma- and sarcotubule-rich myocardial subcellular fractions by cyclic AMP activated intrinsic and extrinsic protein kinases confers upon these membran structures an enhanced ability to bind or take up Ca2+ and that dibutyryl cyclic AMP, like adrenaline, produces in intact cardiac muscle simultaneous increases in contractile force and in the uptake of extracellular Ca2+. These findings are suggestive of a second messenger role of cyclic AMP in the beta-adrenoreceptor-mediated actions of catecholamines on myocardial contractile force and relaxation, in which Ca2+ would serve as a third messenger and be subject, respectively, to more effective removal from its binding sites on troponin. An alternative interpretation regards Ca2+ and cyclic AMP as interdependent twin second messengers in the catecholamine-induced inotropism. Since the physiological meaning of the reported effects of cyclic AMP on isolated myocardial membrane preparations is far from established an instances of a dissociation between the effects of catecholamines on myocardial contractile force and cyclic AMP levels have been observed, there is still room for hypotheses that relegate cyclic AMP to a nonobligatory, at most, supportive role in the action of the catecholamines on cardiac contraction.
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010710:Phosphates / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine
chemical_list: D002395:Catecholamines; D009124:Muscle Proteins; D010710:Phosphates; D000242:Cyclic AMP; D011494:Protein Kinases; D002118:Calcium