Abstract
The response of adenylyl cyclase complex in human atrial tissue removed at corrective surgery of normoxemic and hypoxemic congenital heart defects in children to various stimulants was evaluated and related to the oxygenation state of the myocardium. When comparing response to stimulation in normoxemic and hypoxemic atria a higherbasal as well as stimulated adenylyl cyclase activity was found in hypoxemic atria; an insignificant stimulatory effect of isoprenaline in normoxemic hearts became significant in the atria of hypoxemic patients. Hypoxemic samples also showed two times higher activity when the total catalytic activity was evaluated by the stimulation with forskolin. Higher stimulatory effect of Gpp/NH/p was also observed in hypoxemic than in normoxemic state. Increased adenylyl cyclase activity might represent one of adaptive mechanisms to hypoxemia in patients with congenital heart defects.
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Brodde O-E: β1- and β2 Adrenoceptors in the human heart: Properties, function, and alterations in chronic heart failure. Pharmacol Rev 43: 203–242, 1991
Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove R, Shah P, Jamieson S, Stinson EB: β1- and β2 adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective β1 -receptor down-regulation in heart failure. Circ Res 59: 297–309, 1986
Böhm M, Pieske B, Schnabel P, Schwinger R, Kemkes B, Klovekom W-P, Erdmann E: Reduced effects of doxepamine on force of contractionin the failing human heart despite preserved β2- adrenoceptor subpopulation. J Cardiovascul Pharmacol 14: 549–559, 1989
Dickinson K E J, Nahorski S R: Identification of solubilized beta1 and beta 2 adrenoceptors in mammalian lung. Life Sci 29: 2527–2533, 1981
Hynie S, Šamánek M, Caisedo M, Rožnová L, Hučín B, Vislocký I.: Vliv léčby beta-adrenergnimi blokóry na beta-adrenergni receptory v myokardu dťí s Fallotovou tetralogií. Čas Lék čes 132: 484–488, 1993
Šamánek M, Hučín B, Klenerová V, Hynie S: Effects of hypoxemia on adenylyl cyclase activity in atria and ventricles of children with congenital heart disease. J Mol Cell Cardiol 27: A246, 1995
Šamánek M, Bass A, Ost'adal B, Hucin B, Stejskalová M: Effect of hypoxemia on enzymes supplying myocardial energy in children with congenital heart disease. Internat J Cardiol 25: 265–270, 1989
Lowry O H, Rosenbrough N J, Farr A L, Randall R K: Protein measurement with the Folin phenol. Reagent J Biol Chem 193: 265–275, 1951
Hynie S: Membrane receptors and Transmembrane signalling. Rozpravy Ceskoslovenské Akademie Věd, rocnik 100, Sešit 6, Academia, Praha, 1990
Čpelík J, Hynie S: Inhibitory effects of clonidine and dopamine on adenylate cyclase of rabbit ciliary processes. Curr Eye Res 9: 111–120, 1990
Symons RH: The rapid, simple and improved preparation of high specific activity a[32P] dATP and a[32P] ATP. Nucleic Acid Res 4: 4347–4355, 1977
Birnbaumer L: G proteins in signal transduction. Annu Rev Pharmacol Toxicol 30: 675–705, 1990
Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56: 615–649, 1987
Drummond GE, Severson DL: Cyclic nucleotides and cardiac function. Circ Res 44: 145–153, 1979
Morgan JP: Mechanisms of Disease: Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N E J M 325: 625–632, 1991
Lohse MJ: G-Protein-coupled receptor kinases and the heart. Trends Cardiovasc Med 5: 63–68, 1995
Metzger H, Lindner E: The positive inotropic-acting forskolin, a potent adenylate cyclase activator. Arzneim Forsch 31: 1248–1250, 1982
Strasser RH, Marquetant R: Supersensitivity of the adenylyl cyclase system in acute myocardial ischemia: Evaluation of three independent mechanisms. In: G. Heusch, J. Ross, J. (eds). Supplement to Basic Research in Cardiol 85: Suppl 1, 67–78, 1990
Heusch G, Ross J, Jr Eds: Adrenergic mechanisms in myocardial ischemia. Basic Res Cardiol 85 (suppl. 1): Springer-Verlag New York, 1990
Kozlik-Feldman R, Kramer HH, Wicht H, Feldmann R, Netz H, Reinhardt D: Distribution of myocardial beta-adrenoceptor subtypes and coupling to the adenylate cyclase in children with congenital heart disease and implications for treatment. J Clin Pharmacol 33: 588–595, 1993
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Hynie, S., Klenerová, V., Caicedo, M. et al. Differences in response to activation of adenylyl cyclase by various stimulants in human myocardium. Mol Cell Biochem 163, 329–333 (1996). https://doi.org/10.1007/BF00408673
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DOI: https://doi.org/10.1007/BF00408673