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 cartain of the pathophysiological consequences of chronic alcoholism but few data re availalbe as to the mechanism resonsible 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 reactioins. Soluble fractions of kidney homogenates in teh presnet of > 10 K_m concentratons of NAd exhibited dose dependent loss of specific and total organ PG dehydrogenase activity toward PGE₂ and F_2α. A similar dose dependent decrease in the V_max of the NAD mediated reaction was measured for the oxidation of PGE₁, E₂, and F_2α. Moderate doses of ethanol resulted in an increase in the K_m for PGE₂ and F_2α. K_m 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.