Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium |
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Authors: | C. Devos P. Robberecht P. Nokin M. Waelbroeck M. Clinet J. C. Camus P. Beaufort P. Schoenfeld J. Christophe |
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Affiliation: | (1) Sanofi, Labaz-Sanofi Research Center, 1, Av. de Béjar, B-1120 Brussels, Belgium;(2) Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, 115, Boulevard de Waterloo, B-1000 Brussels, Belgium |
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Abstract: | Summary We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(125I)iodocyanopindolol binding, in the absence and presence of ±-isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for ±-isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, ±-isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The ±-isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.Abbreviations CYP cyanopindolol - Gpp(NH)p 5-guanyl imidodiphosphate - VIP vasoactive intestinal peptide - Ns guanine nucleotide-binding regulatory protein |
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Keywords: | Dog heart Beta-adrenoceptors Adenylate cyclase Heart ischemia |
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