Regulation of Rat Alcohol-Dehydrogenase by Cyclic AMP in Primary Hepatocyte Culture

James John Potter, O. A. Macdougald, Esteban Mezey

Research output: Contribution to journalArticle

Abstract

Alcohol dehydrogenase (ADH) is enhanced separately by epinephrine and by glucagon in primary rat hepatocyte culture. This study determined whether cyclic AMP, a common mediator for some of the actions of the above hormones, increases ADH. Administration of theophylline, a cyclic AMP phosphodiesterase inhibitor which increases endogenous cyclic AMP, in a dose of 100 mg/kg to rats for 5 days, increased ADH activity. Dibutyryl cyclic AMP (10 μM) added to primary hepatocytes in culture increased ADH mRNA and ADH activity at 12 and 24 h, respectively, after its addition. The increase in ADH mRNA was preceded by an increase in the expression of C/EBPβ mRNA and in C/EBPβ protein. Dibutyryl cyclic AMP, in transient transfection experiments of primary rat hepatocyte culture, activated an ADH promoter gene construct containing the C/EBP binding site, but failed to activate a construct containing a 4-bp mutation at this site. These results show that cyclic AMP induces ADH and suggests that this effect is mediated by C/EBPβ binding to the C/EBP site. The previously demonstrated induction of ADH by epinephrine and glucagon may be mediated by a common pathway via an increase in cyclic AMP.

Original languageEnglish (US)
Pages (from-to)329-335
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume321
Issue number2
DOIs
StatePublished - Aug 20 1995

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Alcohol Dehydrogenase
Cyclic AMP
Rats
Hepatocytes
Bucladesine
Glucagon
Messenger RNA
Epinephrine
CCAAT-Enhancer-Binding Proteins
Phosphodiesterase Inhibitors
Theophylline
Cell culture
Transfection
Genes
Binding Sites
Hormones
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Regulation of Rat Alcohol-Dehydrogenase by Cyclic AMP in Primary Hepatocyte Culture. / Potter, James John; Macdougald, O. A.; Mezey, Esteban.

In: Archives of Biochemistry and Biophysics, Vol. 321, No. 2, 20.08.1995, p. 329-335.

Research output: Contribution to journalArticle

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