The effect of methyl-lidocaine on the biosynthesis of phospholipids de novo in the isolated hamster heart.
Methyl-lidocaine is an amphiphilic agent which has been used as an experimental anti-arrhythmic drug. When hamster hearts were perfused with labelled glycerol, the presence of methyl-lidocaine in the perfusate was found to enhance the labelling in phosphatidylserine, phosphatidylinositol, diacylglycerol and triacylglycerol. However, the labelling of phosphatidylcholine and phosphatidylethanolamine was not significantly changed by methyl-lidocaine treatment. Assays in vitro for the enzymes involved in the synthesis of neutral lipids and acidic phospholipids revealed that phosphatidate phosphatase and CTP: phosphatidate cytidylyltransferase activities were stimulated by methyl-lidocaine. The intracellular pool sizes of diacylglycerol and CDP-diacylglycerol were also elevated. We postulate that the enhanced syntheses of the neutral lipids and acidic phospholipids in the methyl-lidocaine-perfused heart were mediated via the direct activation of the key enzymes in the biosynthesis of these lipids de novo.
Tardi
P G
PG
Department of Biochemistry & Molecular Biology and Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Man
R Y
RY
Choy
P C
PC
D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D006224:Cricetinae; D051048:Diacylglycerol O-Acyltransferase; D004075:Diglycerides / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000214:Acyl Coenzyme A; D000889:Anti-Arrhythmia Agents; D004075:Diglycerides; D010743:Phospholipids; D014280:Triglycerides; C014672:N-methyllidocaine; D008012:Lidocaine; D000217:Acyltransferases; D005992:Glycerol-3-Phosphate O-Acyltransferase; D051048:Diacylglycerol O-Acyltransferase; C018764:2-acylglycerophosphate acyltransferase; D009713:Nucleotidyltransferases; C022348:phosphatidate cytidylyltransferase; D010711:Phosphatidate Phosphatase; D002746:Chlorpromazine