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Effect of ß-Adrenoceptor Antagonists on Phospholipid N-Methylation Activities of Cardiac SarcolemmaInstitute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Anatomy and Cell Science, and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Anatomy and Cell Science, and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Anatomy and Cell Science, and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Anatomy and Cell Science, and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Anatomy and Cell Science, and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada Background: Some ß-adrenoceptor antagonists exert a negative inotropic action by affect ing Ca2+ fluxes in the myocardial cell as a consequence of their interaction with sarcolem mal and sarcoplasmic reticular membranes. This action may be caused by their effects on the cliemicophysical properties of membrane 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 pro pranolol, acebutolol, and atcnolol on PE N-methylation in rat heart sarcolemma (SL). Methods and Results: Sarcolemmal membrane was isolated from rat hearts by the hypo- tonic 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 notcd; low concentrations (10-8 M) enhanced the total N-methylation. whereas high con centrations (106 -10-3 M) were inhibitory. Accbutolol (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) methyla tion at site I, whereas accbutolol depressed the SR enzyme activity at site II and atenolol had no effect. The mitochondrial methyltransferase activities at sites I. II, and III were unal tered by any of these drugs. Conclusions: It is suggested that propranolol and acebutolol alter SL and SR PE N-methyl transferase activity at site I and site II, respectively, either by affecting the enzyme directly or by changing the physicochemical properties of the membrane.
Key Words: rat heart • sarcolemma • sarcoplasmic reticulum • mitochondria • phosphatidyleth anolamine N-methylation • ß-adrenergic blocking agents.
Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 3,
239-245 (1998) |
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