Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver

Maria Alfonsina Desiderio, Giuseppe Lugaro, Daniela Galasso, Mario Paolo Colombo

Research output: Contribution to journalArticle

Abstract

Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of ODC gene, demonstrated by nuclear run-on analysis, can account for the accumulation of ODC mRNAs. The involvement of catecholamines in these processes is demonstrated by using prazosin and propranolol, specific antagonists of α1 and β adrenoceptors, respectively. Prazosin reduces almost completely the rise of ODC activity at 4 hr, without affecting mRNA levels. At 16 hr, enzyme activity and mRNAs increase, however, over the values observed in regenerating liver of prazosin-untreated animals. These findings suggest that α1-receptor activation triggers positive control signals for ODC gene expression at the early time of liver regeneration and, on the contrary, negative signals at later times by mainly post-transcriptional and transcriptional mechanisms, respectively. Propranolol reduces similarly the initial 4 hr-rise of ODC activity. These results indicate that activation of both α1- and β-adrenoceptors causes the large increase in ODC activity. Pharmacological manipulation of intracellular Ca2+ levels by verapamil, a Ca2+-channel blocker, or neomycin, an inhibitor of Ca2+ release from endogenous stores, diminishes ODC activity at 4 and 16 hr after PH. ODC mRNA levels, which are not modified at 4 hr, increase over the values of partially hepatectomized rat liver at 16 hr. Trifluoperazine inhibits both ODC activity and mRNA accumulation at the times studied. As a working hypothesis it is proposed that Ca2+mediated processes induced by catecholamines are involved in ODC gene expression during the prereplicative phase of liver regeneration.

Original languageEnglish
Pages (from-to)1605-1613
Number of pages9
JournalBiochemical Pharmacology
Volume40
Issue number7
DOIs
Publication statusPublished - Oct 1 1990

ASJC Scopus subject areas

  • Pharmacology

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