Polyamines in brain and heart of the neonatal rat: effects of inhibitors of ornithine decarboxylase and spermidine synthase.

Published

Journal Article

Daily administration of dicyclohexylamine (DCHA), an inhibitor of spermidine synthase, to neonatal rats produced a dose-dependent depletion of brain spermidine, accompanied by a rise in putrescine and spermine. Despite continued DCHA treatment, levels of all three polyamines returned toward normal within two weeks. alpha-Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, had a much more profound and persistent effect on spermidine and also depleted putrescine throughout drug administration; furthermore, DFMO prevented both the elevation of putrescine caused by DCHA and the eventual restitution of spermidine levels. Although a similar pattern of effects was seen in the heart, the time course of onset of DCHA-induced alterations in polyamine levels and the rapidity of subsequent adaptation were considerably different from those in brain. The net activity of DCHA toward polyamines in developing tissues thus involves the direct actions of the drug on spermidine synthesis in combination with compensatory metabolic adjustments made by each tissue to polyamine depletion.

Full Text

Duke Authors

Cited Authors

  • Slotkin, TA; Bartolome, J; Persons, D; Whitmore, WL

Published Date

  • September 3, 1984

Published In

Volume / Issue

  • 35 / 10

Start / End Page

  • 1125 - 1131

PubMed ID

  • 6434889

Pubmed Central ID

  • 6434889

International Standard Serial Number (ISSN)

  • 0024-3205

Digital Object Identifier (DOI)

  • 10.1016/0024-3205(84)90078-x

Language

  • eng

Conference Location

  • Netherlands