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

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Adrenergic Antagonists
Ornithine Decarboxylase
Liver
Adrenergic Agents
Rats
Messenger RNA
Prazosin
Liver Regeneration
Hepatectomy
Gene expression
Propranolol
Adrenergic Receptors
Catecholamines
Chemical activation
Gene Expression
Trifluoperazine
Neomycin
Enzyme activity
Verapamil
Regeneration

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver. / Desiderio, Maria Alfonsina; Lugaro, Giuseppe; Galasso, Daniela; Colombo, Mario Paolo.

In: Biochemical Pharmacology, Vol. 40, No. 7, 01.10.1990, p. 1605-1613.

Research output: Contribution to journalArticle

Desiderio, Maria Alfonsina ; Lugaro, Giuseppe ; Galasso, Daniela ; Colombo, Mario Paolo. / Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver. In: Biochemical Pharmacology. 1990 ; Vol. 40, No. 7. pp. 1605-1613.
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