Effect of DL-α-hydrazino-δ-aminovaleric acid, an inhibitor of ornithine decarboxylase, on polyamine metabolism in isoproterenol-stimulated mouse parotid glands

Hideo Inoue, Yukio Kato, Masaharu Takigawa, Kozaburo Adachi, Yoshiro Takeda

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The effects of DL-α-hydrazino-δ-aminovaleric acid (DL-HAVA) on polyamine metabolism in isoproterenol(IPR)-stimulated mouse parotid glands were investigated both in vitro and in vivo.Using partially purified enzyme preparations, it was found that DL-HAVA strongly inhibited ornithine decarboxylase [EC 4.1.1.17] by competing with L-ornithine. Other enzymes metabolizing ornithine and pyridoxal phosphate-dependent enzymes were at least 2-3 orders of magnitude less sensitive to DL-HAVA than ornithine decarboxylase.Administration of DL-HAVA greatly depressed the increases in both the putrescine level and putrescine formation from L-ornithine induced by IPR in the mouse parotid glands. Under the same conditions, the stimulation of DNA synthesis and subsequent cell proliferation in the glands were also suppressed. However, the IPR-dependent increases in S-adenosyl-L-methionine decarboxylase [EC 4.1.1.50] activity, synthesis and the tissue concentration of spermidine, and RNA synthesis in the parotid glands were not affected appreciably by DL-HAVA.The inhibition of DNA synthesis by DL-HAVA was effectively prevented by putrescine, but not by spermidine or 1,7-diaminoheptane, given at the time when dl-HAVA inhibited stimulation of putrescine formation by IPR. From these results, it is proposed that putrescine is involved in cell proliferation besides being a precursor of spermidine.The effects of methylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosyl-L-methionine decarboxylase, on the metabolism of polyamines and nucleic acids in growing parotid glands were also examined.

Original languageEnglish
Pages (from-to)879-893
Number of pages15
JournalJournal of biochemistry
Volume77
Issue number4
DOIs
Publication statusPublished - Apr 1975
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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