Modification of the β-Adrenergic Mechanisms in Myocardium by Divalent Cations
Irrespective of the type and nature of stressful stimulus, elevated levels of circulating catecholamines are commonly observed. A small amount of catecholamines released in acute and mild stress is considered to increase heart function beneficially by binding to the β-adrenergic receptors, activating the adenylate cyclase system and raising the intracellular concentration of calcium (1,2). In this regard it should be mentioned that β-adrenergic receptors are coupled to adenylate cyclase by guanine nucleotide binding protein, and their activation by catecholamines is associated with formation of cyclic AMP, phosphorylation of Ca2+-channels through protein kinase and subsequent increase in the entry of Ca2+ into the myocardial cell. On the other hand, an excessive amount of catecholamine released in chronic and severe stress is believed to produce cardiotoxic effects which are associated with the occurrence of an intracellular Ca2+ overload and abnormalities in the excitation-contraction coupling process (3,4,5). Although participation of the β-adrenergic receptor-adenylate cyclase mechanism in raising the intracellular concentration of calcium is obvious at initial stages, its role in later stages with prolonged exposure of the myocardium to high doses of catecholamines is not clear at present. This view is based on the fact that prolonged exposure of tissue to catecholamines has been shown to produce desensitization of adrenergic receptors (6,7,8).
KeywordsDivalent Cation Adrenergic Receptor Cyclase Activity Adenylate Cyclase Activity Guanine Nucleotide Binding Protein
Unable to display preview. Download preview PDF.
- 3.Fleckenstein A, Janke J, Doring HJ, Pachinger O: Ca overload as the determinant factor in the production of catecholamine-induced myocardial lesions. Rec Adv Stud Card Struc Met 2: 455–466, 1973.Google Scholar
- 5.Dhalla NS, Dzurba A, Pierce GN, Tregaskis MJ, Panagia V, Beamish RE: Membrane changes in myocardium during catecholamine-induced pathological hypertrophy. Persp Cardiovas Res 7: 527–534, 1983.Google Scholar
- 14.McConnaughey MM, Jones LR, Watanabe AM, Besch HR, Jr, Williams LT, Lefkowitz RJ: Thyroxine and propylthiouracil effects on alpha- and beta-adrenergic receptor number, ATPase activities and sialic acid content of rat cardiac membrane vesicles. J Cardiovasc Pharmacol 1: 609–623, 1979.PubMedCrossRefGoogle Scholar