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Circulation Research. 1990;66:28-36

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Circulation Research, Vol 66, 28-36, Copyright © 1990 by American Heart Association

ARTICLES

Stimulation of phospholipid N-methylation by isoproterenol in rat hearts

Y Taira, V Panagia, KR Shah, RE Beamish and NS Dhalla
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.

Phosphatidylethanolamine (PtdEtn) N-methyltransferase activities were studied in rat heart sarcolemmal and sarcoplasmic reticular fractions after a single intraperitoneal injection of isoproterenol (0.5-5.0 mg/kg). Three active sites (I, II, and III) for PtdEtn N-methylation were assayed by measurement of [3H]methyl group incorporation from 0.055, 10, and 150 microM S-adenosyl-L-[methyl-3H]methionine into membrane PtdEtn molecules. Total methylation activity for catalytic site I of both sarcolemma and sarcoplasmic reticulum was stimulated within 2 minutes by isoproterenol in a dose-dependent manner. Although the increased methyltransferase activity in sarcoplasmic reticulum was normalized at 10 minutes, the enzyme activity in sarcolemma was normalized at 5 minutes but was again increased at 10-30 minutes after isoproterenol injection. No changes in response to isoproterenol were seen for site II and III N-methylation activities in either membrane. Individual N-methylated phospholipids (phosphatidyl-N- monomethylethanolamine, phosphatidyl-N,N-dimethylethanolamine, and phosphatidylcholine), which specifically formed at each site, showed similar behavior. Pretreatment of the animals with a beta-blocking drug, atenolol, for 2 days prevented the isoproterenol-induced changes in hemodynamic parameters and sarcolemmal methylation without affecting the enhanced methylation activities in sarcoplasmic reticulum. In vitro addition of cyclic AMP-dependent protein kinase (catalytic subunit) plus Mg-ATP enhanced methyltransferase activities in sarcolemma and sarcoplasmic reticulum from control hearts by 2.7- and 2.3-fold, respectively; however, under the same in vitro conditions, only about 20% activation was seen in both subcellular membranes isolated from the heart of isoproterenol-injected animals.(ABSTRACT TRUNCATED AT 250 WORDS)


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V. Panagia, Y. Taira, G. L. Bryson, P. S. Tappia, and N. S. Dhalla
Effect of {beta}-Adrenoceptor Antagonists on Phospholipid N-Methylation Activities of Cardiac Sarcolemma
Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1998; 3(3): 239 - 245.
[Abstract] [PDF]


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