Summary
The purpose of this study was to explore alterations in the life cycle of adrenergic receptors and the Gs protein in the heart of ischemic animals. In initial experiments left anterior descending coronary artery occlusion was performed in guinea pigs. Sarcolemmal (SL) and light vesicle (LV) (presumably intracellular) fractions were prepared. Both fractions contained a substantial number of β-adrenergic receptors and α1-adrenergic receptors: the relative proportion of β-adrenergic receptors in LV/SL was greater than for α1-adrenergic receptors. Myocardial ischemia produced a rapid externalization of β-adrenergic receptors from LV to SL. α1-adrenergic receptors also increased in SL but without an apparent externalization from LV. Pretreatment of animals with either the non-selective β-antagonist Propranolol or the β1-selective antagonist atenolol increased the number of SL β-receptors and blunted the ischemia-induced increase in SL β-adrenergic receptors. Treatment with the partial agonist pindolol did not cause up-regulation of β-receptors, and did not block ischemia-induced externalization.
In the second part of this study, we have begun to examine post-receptor events in a rat model of myocardial ischemia. Ligation of the distal left main coronary artery in the rat led to an increase in SL β-receptors. As G proteins play a pivotal role in transducing receptor occupancy to activation of effector molecules, we measured levels of Gs which stimulates adenylate cyclase activity, using an ELISA technique. In rat SL the amount of αs markedly decreased within 15 min of coronary occlusion. There was no transfer of Gs activity to the light vesicle fraction.
These studies indicate the dynamic nature of adrenergic receptors and the αs protein in the sarcolemma in myocardial ischemia. Changes in adrenergic receptor number and in G protein expression may contribute to the altered pathophysiology of the ischemic heart.
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© 1991 Springer-Verlag Berlin Heidelberg
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Maisel, A.S., Ransnäs, L.A., Insel, P.A. (1991). β-Adrenergic Receptors and the Gs Protein in Myocardial Ischemia and Injury. In: Heusch, G., Ross, J. (eds) Adrenergic Mechanisms in Myocardial Ischemia. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-11038-6_4
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DOI: https://doi.org/10.1007/978-3-662-11038-6_4
Publisher Name: Steinkopff, Heidelberg
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