Kinetic changes in rat renal 15-hydroxy-prostaglandin dehydrogenase induced by chronic ethanol exposure.
Several lines of investigation have suggested that exposure to ethanol may lead to alterations in both the synthesis and degradation of the E and F series of prostaglandins (PG). It has been suggested that these changes in PG metabolism underlie certain of the pathophysiological consequences of chronic alcoholism but few data are available as to the mechanism responsible for these changes. We now report that chronic exposure to ethanol in moderate doses (17% total dietary calories as ethanol) and high doses (35% total dietary calories as ethanol) results in a concentration dependent loss of renal 15-hydroxy-prostaglandin dehydrogenase for the NAD mediated reactions. Soluble fractions of kidney homogenates in the presence of greater than 10 Km concentrations of NAD exhibited dose dependent loss of specific and total organ PG dehydrogenase activity toward PGE2 and F2 alpha. A similar dose dependent decrease in the Vmax of the NAD mediated reaction was measured for the oxidation of PGE1, E2, and F2 alpha. Moderate doses of ethanol resulted in an increase in the Km for PGE2 and F2 alpha. Km values for the NADP mediated reactions were not significantly influenced by exposure to high doses of ethanol other than for PGE1. These data suggest that chronic ethanol consumption results in a dose dependent, selective inhibition of the metabolism of PGs of the "2" series by the renal PGDH enzyme which utilizes NAD.
D000818:Animals; D015232:Dinoprostone; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D009243:NAD; D009249:NADP; D011458:Prostaglandins E; D051381:Rats; D013379:Substrate Specificity
D011458:Prostaglandins E; D009243:NAD; D000431:Ethanol; D009249:NADP; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone