Effects of ethanol on prostanoid production by liver fat-storing cells.
Fat-storing cells participate in the development of alcoholic liver disease. To study possible effects of ethanol on prostaglandin metabolism by fat-storing cells, we isolated them from normal rat liver. Cultured fat-storing cells produced substantial amounts (DNA, about 2 ng/micrograms every 24 hr) of prostaglandin E2 and prostaglandin I2 (measured as 6-keto prostaglandin F1 alpha) but no significant amounts of prostaglandin F2 alpha. This production was markedly enhanced by the addition of ethanol in concentrations likely to occur in the blood during alcohol consumption. We confirmed the presence of class 1 alcohol dehydrogenase activity and isoenzymes in the cytosol of cultured fat-storing cells in their second passage. The stimulatory effect of ethanol was inhibited by 4-methylpyrazole (an alcohol dehydrogenase inhibitor), exaggerated by disulfiram (an aldehyde dehydrogenase inhibitor) and reproduced by concentrations of acetaldehyde likely to occur in the liver. Thus, our results indicate that fat-storing cells produce vasodilatory prostaglandins and that this production is enhanced by the acetaldehyde that results from the oxidation of ethanol catalized by alcohol dehydrogenase present in these cells.
Flisiak
R
R
Alcohol Research and Treatment Center, Veterans Affairs Medical Center, Bronx, New York 10468.
Baraona
E
E
Li
J
J
Lieber
C S
CS
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000079:Acetaldehyde / Q000494:pharmacology; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis*; D004221:Disulfiram / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D007527:Isoenzymes / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D011720:Pyrazoles; D000431:Ethanol; D015121:6-Ketoprostaglandin F1 alpha; D000077604:Fomepizole; D011464:Epoprostenol; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde; D015232:Dinoprostone; D004221:Disulfiram