Metabolic fate of [14C]-ethanol into endothelial cell phospholipids including platelet-activating factor, sphingomyelin and phosphatidylethanol.
The metabolic fate of ethanol into the phospholipid pool of calf pulmonary artery endothelial cells was studied. [14C]-ethanol was incorporated into various endothelial cell phospholipids including phosphatidylethanol (PEth), which may represent a substantial fraction in microdomains of membrane phospholipids. The incorporation into phospholipids was reduced in the presence of pyrazole and cyanamide, inhibitors of ethanol metabolism. Wortmannin, the phosphatidylinositol 3-kinase inhibitor, increased [14C]-PEth formation. [3H]-acetate was also incorporated into endothelial cell phospholipids but in a different pattern. Distribution of [3H]-acetate and [14C]-ethanol into the fatty acyl moiety versus the glycerophosphoryl backbone of the phospholipids was also different. Stimulation of the endothelial cells with ATP increased [3H]-acetate incorporation into platelet-activating factor (PAF) and ethanol decreased it. Ethanol exposure increased ATP-stimulated [3H]-acetate incorporation into sphingomyelin. However, ATP had no effect on the incorporation of [14C]-ethanol into any phospholipids. The results suggest that the two precursors contribute to a separate acetate pool and that the sphingomyelin cycle may be sensitized in ethanol-treated cells. Thus, metabolic conversions of ethanol into lipids and the effect of ethanol on specific lipid mediators, e.g PAF, PEth and sphingomyelin, may be critical determinants in the altered responses of the endothelium in alcoholism.
Magai
R M
RM
Department of Pharmacology, University of Missouri School of Medicine, 1 Hospital Drive, Columbia, MO 65212, USA.
Shukla
S D
SD
D019342:Acetic Acid / Q000493:pharmacokinetics; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000431:Ethanol / Q000493:pharmacokinetics*; D020404:Glycerophospholipids / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D010972:Platelet Activating Factor / Q000096:biosynthesis; D013109:Sphingomyelins / Q000096:biosynthesis; D013997:Time Factors; D014316:Tritium
D002250:Carbon Radioisotopes; D020404:Glycerophospholipids; D010743:Phospholipids; D010972:Platelet Activating Factor; D013109:Sphingomyelins; C051521:phosphatidylethanol; D014316:Tritium; D000431:Ethanol; D019342:Acetic Acid