BACKGROUND: Some beta-adrenoceptor antagonists exert a negative inotropic action by affecting Ca(2+) fluxes in the myocardial cell as a consequence of their interaction with sarcolemmal and sarcoplasmic reticular membranes. This action may be caused by their effects on the chemicophysical properties of membranes phospholipids. Because phosphatidylethanolamine (PE) N-methylation can influence the chemicophysical properties of membranes, these agents may affect PE N-methylation. This study was undertaken to examine the effects of propranolol, acebutolol, and atenolol on PE-N-methylation in rat heart sarcolemma (SL). METHODS AND RESULTS: Sarcolemmal membrane was isolated from rat hearts by the hypotonic shock LiBr method. Incorporation of radiolabeled methyl groups from S-adenosyl-l-methionine was assayed at three catalytic sites involved in the PE N-methylation reaction in the presence and absence of these drugs. A biphasic effect of propranolol at site I was noted; low concentrations (10(-8) M) were inhibitor. Acebutolol (10(-9)-10(-3) M) depressed methyl group incorporation in SL at site II in a dose-dependent manner, whereas atenolol showed no effect. Propranolol also exerted a biphasic effect on sarcoplasmic reticular (SR) methylation at site I, whereas acebutolol depressed the SR enzyme activity at site II and atenolol had no effect. The mitochondrial methyltransferase activities at sites I, II, and III were unaltered by any of these drugs. CONCLUSIONS: It is suggested that propranolol and acebutolol alter SL and SR PE N-methyltransferase activity at site I and site II, respectively, either by affecting the enzyme directly or by changing the physiochemical properties of the membrane.
BACKGROUND: Some beta-adrenoceptor antagonists exert a negative inotropic action by affecting Ca(2+) fluxes in the myocardial cell as a consequence of their interaction with sarcolemmal and sarcoplasmic reticular membranes. This action may be caused by their effects on the chemicophysical properties of membranes phospholipids. Because phosphatidylethanolamine (PE) N-methylation can influence the chemicophysical properties of membranes, these agents may affect PE N-methylation. This study was undertaken to examine the effects of propranolol, acebutolol, and atenolol on PE-N-methylation in rat heart sarcolemma (SL). METHODS AND RESULTS: Sarcolemmal membrane was isolated from rat hearts by the hypotonic shock LiBr method. Incorporation of radiolabeled methyl groups from S-adenosyl-l-methionine was assayed at three catalytic sites involved in the PE N-methylation reaction in the presence and absence of these drugs. A biphasic effect of propranolol at site I was noted; low concentrations (10(-8) M) were inhibitor. Acebutolol (10(-9)-10(-3) M) depressed methyl group incorporation in SL at site II in a dose-dependent manner, whereas atenolol showed no effect. Propranolol also exerted a biphasic effect on sarcoplasmic reticular (SR) methylation at site I, whereas acebutolol depressed the SR enzyme activity at site II and atenolol had no effect. The mitochondrial methyltransferase activities at sites I, II, and III were unaltered by any of these drugs. CONCLUSIONS: It is suggested that propranolol and acebutolol alter SL and SR PE N-methyltransferase activity at site I and site II, respectively, either by affecting the enzyme directly or by changing the physiochemical properties of the membrane.