Alterations of Phosphatidylethanolamine N-Methylation in Rat Heart by Quinidine

doi:10.1097/00005344-198911000-00013

Paper

Alterations of Phosphatidylethanolamine N-Methylation in Rat Heart by Quinidine

Published Nov 1, 1989 · V. Panagia, P. Ganguly, Mahesh P. Gupta

Journal of Cardiovascular Pharmacology

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8

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0

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Abstract

Summary: To elucidate the molecular mechanism underlying the adverse depression of myocardial contractility observed during antiarrhythmic therapy of quinidine, we investigated its action on the phosphatidylethanolamine N-methyltransferase (EC 2.1.1.17) activities of cardiac subcellular membranes. Rat heart sarcolemma, mitochondria, and microsomes (sarcoplasmic reticular fragments) were isolated, and the three catalytic sites for N-methylation activities were examined with 0.055 (site I), 10 (site II), and 150 (site III) μM concentrations of S-adenosyl-l-[methyl-3H]methionine as a methyl donor. Total methyl group incorporation into sarcolemmal phosphatidylethanolamine was depressed by 10−6–10−3 M quinidine at sites II and III. The activity of site I was stimulated at low (10−9 M) concentrations and inhibited at high concentrations of the drug. A similar behaviour was observed with procainamide, although the inhibitory effect was less pronounced and was not additive with quinidine. Quinidine-induced inhibition was associated with a depression of Vmax, while the apparent affinity for S-adenosyl-l-methionine was unaltered. Analysis of individual methylated phospholipids confirmed inhibition by quinidine at sites II and III in sarcolemma. Microsomal phosphatidylethanolamine N-methylation was affected by 10−6M quinidine only at site II, whereas no changes were noted in mitochondria. Quinidine also inhibited both the positive inotropic response and concomitant increase in tissue N-methylated phospholipids observed upon l-methionine perfusion of rat heart. These results suggest that quinidine alters the intramembranal level of N-methylated phospholipids, and this may serve as a biochemical mechanism contributing to its negative inotropic effect.

In Vitro Study

Study Snapshot

Quinidine alters the intramembranal level of N-methylated phospholipids in rat hearts, potentially contributing to its negative inotropic effect during antiarrhythmic therapy.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Alterations of Phosphatidylethanolamine N-Methylation in Rat Heart by Quinidine

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References

Citations

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