Methionine-Induced Positive Inotropic Effect in Rat Heart

Possible Role of Phospholipid N-Methylation

Panagia, Vincenzo
Gupta, Mahesh P.
Ganguly, Pallab K.
Dhalla, Naranjan S.

From the Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Departments of Anatomy and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.

Supported by a grant from the Manitoba Heart Foundation. V.P. was a scholar of the Manitoba Heart Foundation.

Address for correspondence: V. Panagia, MD, PhD, Associate

Professor, Department of Anatomy, Faculty of Medicine, University of Manitoba, Winnipeg, Canada, R3E 0W3.

Received January 5, 1987; accepted July 20, 1987.

Circulation Research 62(1):p 51-55, January 1988.

Perfusion of isolated rat heart with L-methionine produced a positive inotropic effect that was temporally preceded, as well as accompanied, by an increase of methyl group incorporation into N-methylated phospholipids of the myocardium. Maximal increase in contractile force development was associated with maximal methyl group incorporation. Both parameters showed a dose-related dependence on methionine and correlated positively (r = 0.965) upon regression analysis of the data. The presence of adenosine, L-homocysteine thiolactone and erythro-9-(2-hydroxy-3-nonyl) adenine in the perfusion medium inhibited the positive inotropic effect as well as the incorporation of methyl groups into phospholipids. Cycloleucine, an inhibitor of S-adenosylmethionine synthetase, also reduced the increase in contractility by methionine. Methionine-induced positive inotropic effect could be modulated by varying Ca²⁺ concentration in the perfusate and was inhibited by ryanodine, a blocker of sarcoplasmic reticular Ca²⁺ release. These observations indicate that L-methionine may serve as a powerful positive inotropic agent and suggest that phospholipid N-methylation plays an important role in functional activity of rat heart.