The effect of lidocaine on de novo phospholipid biosynthesis in the isolated hamster heart.
Lidocaine is used clinically as an antiarrhythmic agent, but its effect on cardiac phospholipid metabolism has not been defined. In this study, hamster hearts were perfused with [1,3-3H]glycerol in the presence of 0.5 mg/mL lidocaine. The incorporation of radioactivities into lysophosphatidic acid, phosphatidic acid, phosphatidylethanolamine, cytidine diphosphate diacylglycerol, phosphatidylinositol, phosphatidylserine, diacylglycerol and triacylglycerol were enhanced by lidocaine treatment, whereas the labelling of phosphatidylcholine was reduced. Analyses of enzyme activities in the heart after perfusion with lidocaine revealed that the activities of phosphatidate phosphatase and acyl-coenzyme A (CoA):1,2-diacylglycerol acyltransferase were enhanced. The presence of lidocaine in the assay did not directly stimulate these enzymes. However, the activity of acyl-CoA:glycerol-3- phosphate acyltransferase was stimulated by lidocaine whereas the activity of cytidine diphosphocholine:1,2-diacylglycerol cholinephosphotransferase was inhibited by lidocaine. We conclude that lidocaine affects the regulation of phospholipid biosynthesis in the heart by both direct and indirect modulation of phospholipid biosynthetic enzymes.
Wong
J T
JT
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Man
R Y
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Choy
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PC
D000818:Animals; D006224:Cricetinae; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology*; D008647:Mesocricetus; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D010743:Phospholipids / Q000096:biosynthesis*; D014316:Tritium
D010743:Phospholipids; D014316:Tritium; D008012:Lidocaine; D005992:Glycerol-3-Phosphate O-Acyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D005990:Glycerol