Puromycin inhibition of ethanol ingestion and liver alcohol dehydrogenase activity in the rat

Factors that modify the metabolism of ethanol in rat liver and adaptive changes produced by its chronic administration

“…Although in the first weeks of treatment there was a good correlation between alcohol dehydrogenase activity and ethanol metabolism, Hawkins et al (1966) found that with longer treatment (up to 12 weeks) the rate of ethanol disappearance in vivo increased substantially more than could be explained by the increase in alcohol dehydrogenase activity. Several authors have described an increased alcohol dehydrogenase activity after chronic ethanol treatment in rats and mice (Dajani, Danielski & Orten, 1963;McClearn, Bennett, Herbert, Kakihana & Schlesinger, 1964; Mendelson, Mello, Corbett & Ballard, 1965;Mistilis & Birchall, 1969); unfortunately in most of these studies no correlation was made between alcohol dehydrogenase activity and the rate of ethanol disappearance in vivo or in vitro. A large number of authors have, conversely, found no change in the liver alcohol dehydrogenase after chronic administration of ethanol (Aebi & von Wartburg, 1960; von Wartburg & Rothlisberger, 1961;Figueroa & Klotz, 1964;Greenberger, Cohen & Isselbacher, 1965;Ugarte, Pino & Insunza, 1967).…”

Effect of ethanol administration on alcohol dehydrogenase activity in mouse hepatic cells: ultracytochemical study.

“…In addition, Fujisawa (19) found that in rats receiving 20% ethanol solution as sole drinking fluid plus 5 g ethanol/kg of body weight two times a week intragastrically, there was the 42% and 109% increases in liver ADH activity as compared with that of the controls, at 2 and 4 weeks respectively. Mendelson et al (49) reported an increase in liver ADH activity in the rat following a 26 days exposure to 10% ethanol in drinking water. Mirone (51) reported that C57BLJ6J mice given 15% ethanol as the sole drinking fluid showed a highly significant increase in liver ADH activity at 3 and 5 months, but not at 12 months.…”

“…Why has induction of ADH activity, found in this study after long-term ethanol administration by intubation (2.4 g/kg of body weight), been produced? With regard to this matter, Mendelson et al (49) showed that induced increases in liver ADH activity following long-term ethanol administration were significantly suppressed by puromycin which is an effective agent for blocking some step in the transfer of amino acid from soluble RNA into protein (20) . Furthermore, Mistilis and co-workers (52,53) suggested that the increase in ADH levels in ethanol-fed animal was the result of de novo protein synthesis, because the administration of actinomycin D, which is known to inhibit nucleic acid synthesis, and cycloheximide, which blocks protein synthesis at the ribosomal level, prevented the rise in ADH activity.…”

“…As mentioned above, ADH level in the ethanol-preferring rats is opposite to that in the ethanol-preferring mice. However, Mendelson et al (49) showed that adaptive increases in ADH activity in rats may be suppressed by puromycin and concomitant ingestion of ethanol was also suppressed. Furthermore, recent study has demonstrated a parallel strain difference in voluntary ethanol consumption and in ADH activity in rats (47).…”

“…Some investigators (11,12,19,26,49,51,52,53,57) observed an increase in ADH activity after long-term intake of ethanol, whereas others reported no change (6,13,21,24,50,78,79) or a decrease (21,35). Therefore, whether ADH activity is increased by long-term intake of ethanol has been a matter of dispute.…”