Chlorpromazine and human platelet glycerolipid metabolism: precursor specificity and significance of drug-platelet interaction time.
Chlorpromazine is known to have a number of effects on glycerolipid metabolism in a variety of cell types, and in some cases reports are contradictory. To investigate the basis for some of these discrepancies, we reinvestigated the effects of chlorpromazine on some aspects of platelet glycerolipid metabolism. Time-courses conducted with [3H]glycerol or [3H]palmitic acid showed that the effects of chlorpromazine on the labelling of phosphatidylcholine, diacylglycerol, and triacyglycerol were highly dependent upon platelet-drug interaction time. The time-dependent changes in labelling patterns were independent of the presence of radiolabel during incubation, and were not the results of time-dependent changes in the platelets per se. The effects of chlorpromazine on the labelling of platelet glycerolipids by [3H]glycerol, [3H]palmitic acid, [32P]P(i) ([32P]phosphatase), and [14C]choline were compared. Dose-response curves conducted at 30-min incubation time showed that chlorpromazine potently inhibited labelling of diacylglycerol and diacyglycerol-derived lipids (triacyglycerol and phosphatidylcholine) by the 3H-labelled precursors. Labelling of phosphatidylcholine by [32P]P(i) or [14C]choline was, however, not affected at all by the drug. We conclude that the effects of chlorpromazine on platelets are highly time-dependent, and that the prolonged effects are most likely to be of biological significance. Furthermore, in platelets the effects of the drug on the labelling of phosphatidylcholine by isotope-labelled precursors are highly dependent on the route of incorporation of the specific precursor chosen.
Department of Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway. Knut.Olav.Daasvatn@pki.uib.no
K O
KO
Daasvatn
H
H
Holmsen
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002746:Chlorpromazine / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D019308:Palmitic Acid / Q000378:metabolism*; D010640:Phenothiazines / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D004075:Diglycerides; D010640:Phenothiazines; D010713:Phosphatidylcholines; D014280:Triglycerides; D014316:Tritium; D019308:Palmitic Acid; D011433:Propranolol; C031637:phenothiazine; D002794:Choline; D005990:Glycerol; D002746:Chlorpromazine