Effects of ischemia on the canine myocardial beta-adrenoceptor-linked adenylate cyclase system.
Several studies indicate that myocardial ischemia causes a redistribution of beta-adrenergic receptors from a presumably intracellular compartment to the cell surface. However, a decreased adenylate cyclase and contractile responsiveness to beta-adrenergic stimuli has also been reported. The aim of the present study was to investigate possible ischemia-induced changes in myocardial beta-adrenoceptor coupling to adenylate cyclase. Myocardial ischemia was induced by hydraulic occlusion of the LAD in mongrel dogs anesthetized with isoflurane. After 90 min of ischemia, tissue samples were removed from the ischemic and nonischemic regions for tissue catecholamine determinations and for the preparation of particulate fractions from tissue homogenates. Saturation experiments on microsomal fractions obtained from the ischemic and control areas did not reveal any significant changes in the calculated dissociation constant for (-)[125I]iodocyanopindolol binding nor in the calculated receptor density. Likewise, the relative numbers of beta 2-adrenergic receptors were comparable in both preparations (approximately 20%). On the other hand, the proportion of beta-adrenoceptors stabilized in the high-affinity state by (-)isoproterenol was significantly reduced in the ischemic region when compared with the control myocardium (17 +/- 5 vs. 41 +/- 4%). This change was accompanied by a significant decrease in the intrinsic activity of (-)isoproterenol in stimulating adenylate cyclase activity. We propose that the initial uncoupling of the beta-adrenoceptor from its effector is a physiologically important, protective mechanism which guards the ischemic myocardium against the deleterious effect of excessive sympathetic stimulation.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; C026777:ICI 118551; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine