The purpose of this research proposal is to continue our investigations into the basic mechanisms by which the catecholamines affect cellular functions. Particular model systems to which the overall theme of the research program will be addressed include those that have been informative in previous work of this laboratory. They are the developing rat reticulocyte and the turkey erythrocyte. This inquiry will utilize techniques which are pertinent to membrane-associated effects of the catecholamines: the detection and function of beta-adrenergic receptors; detection and function of guanine nucleotide binding sites; adenylate cyclase activity; cyclic AMP levels; and cation fluxes. In a related area, the radioreceptor assay for propranolol will be used to explore selected aspects of the pharmacokinetics of beta-adrenergic inhibitors. Specific areas to be explored are a) functional and quantitative aspects of the beta adrenergic receptor in rat reticulocytes and erythrocytes; b) the mechanism of action and identification of a cellular activator of catecholamine-dependent adenylate cyclase in rat erythroid cells; c) the role of the cellular activator in the membrane-associated changes that accompany maturation of the rat reticulocytes; d) the effect of thyroid hormone on the beta receptor complex and beta-adrenergic-dependent cation transport in the turkey erythrocyte; e) the actions of thyroid hormone on the active transport system in the turkey erythrocyte; and f) plasma correlates of clinical beta-adrenergic blockade. The basic objective is to understand further the role of beta receptors and the processes to which they are coupled in the overall regulation of the effects of the catecholamines. The clinical objective of this proposal is to apply and refine basic research tools to problems of clinical importance such as the relationship between thyroid hormone and the catecholamines and the pharmacokinetics of the active forms of propranolol.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Pharmacology A Study Section (PHRA)
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Morris, S A; Tanowitz, H; Makman, M et al. (1992) Trypanosoma cruzi: alteration of cAMP metabolism following infection of human endothelial cells. Exp Parasitol 74:69-76
Morris, S A; Horn, E M; Hawley, T et al. (1991) The influence of detergents on the availability of pertussis toxin substrates. Arch Biochem Biophys 290:86-92
Morris, S A; Barr, S; Weiss, L et al. (1991) Myocardial beta-adrenergic adenylate cyclase complex in a canine model of chagasic cardiomyopathy. Circ Res 69:185-95
Han, H M; Bilezikian, J P; Robinson, R B (1990) Functional uncoupling of the inhibitory alpha 1-adrenergic response from a G-protein in innervated cultured cardiac cells by K+ depolarization. J Mol Cell Cardiol 22:49-56
Morris, S A; Wittner, M; Weiss, L et al. (1990) Extracellular matrix derived from Trypanosoma cruzi infected endothelial cells directs phenotypic expression. J Cell Physiol 145:340-6
Morris, S A; Tanowitz, H B; Wittner, M et al. (1990) Pathophysiological insights into the cardiomyopathy of Chagas' disease. Circulation 82:1900-9
Horn, E M; Bilezikian, J P (1990) Mechanisms of abnormal transmembrane signaling of the beta-adrenergic receptor in congestive heart failure. Circulation 82:I26-34
Han, H M; Robinson, R B; Bilezikian, J P et al. (1989) Developmental changes in guanine nucleotide regulatory proteins in the rat myocardial alpha 1-adrenergic receptor complex. Circ Res 65:1763-73
Horn, E M; Johnson, N J; Bilezikian, J P et al. (1989) Developmental changes in the electrophysiological properties and the beta-adrenergic receptor-effector complex in atrial fibers of the canine coronary sinus. Circ Res 65:325-33
Morris, S A; Weiss, L M; Factor, S et al. (1989) Verapamil ameliorates clinical, pathologic and biochemical manifestations of experimental chagasic cardiomyopathy in mice. J Am Coll Cardiol 14:782-9

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