Methionine-induced positive inotropic effect in rat heart: possible role of phospholipid N-methylation.
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.
Panagia
V
V
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Gupta
M P
MP
Ganguly
P K
PK
Dhalla
N S
NS
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology
D010743:Phospholipids; D012433:Ryanodine; C010192:9-(2-hydroxy-3-nonyl)adenine; D008715:Methionine; D000225:Adenine; D002118:Calcium