Continuous infusion of ethanol-containing diets has been demonstrated to ge
nerate well-defined pulses in blood and urine ethanol concentrations that o
ccur with a frequency of approximately 6 days. The present study aimed to d
etermine if hepatic class I alcohol dehydrogenase was the cause of these cy
cles. Adult male rats were fed an ethanol-containing diet by continuous int
ragastric infusion. Hepatic ADH activity, class I ADH mRNA level and rate o
f class I ADH gene transcription fluctuated in a cyclic pattern that positi
vely correlated with UECs, and inhibition of ADH with 4-methylpyrazole abol
ished the UEC pulses. These data demonstrate for the first time an ethanol-
dependent regulation of rat hepatic class I ADH. The cyclic behavior of the
ethanol levels correlates with changes in class I ADH expression and impli
es adaptability of the ethanol eliminating system to high concentrations of
alcohol. (C) 2000 Academic Press.