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Polyamine reutilization and turnover in brain
Authors:Nikolaus Seiler  Frank N Bolkenius
Institution:(1) Merrell-Dow Research Institute Strasbourg Center, 16 rue d'Ankara, 67084 Strasbourg, France
Abstract:N1, N2-bis-(2, 3-butadienyl)-1, 4-butanediamine (MDL 72527) is an irreversible, specific inhibitor of polyamine oxidase, which allows one to completely inactivate this enzyme in all organs of an experimental animal. As a result one observes a linear increase of N1-acetylsperimidine and N1-acetylspermine concentrations in brain. The rate of accumulation seems directly proportional to the rate of spermidine, and spermine degradation respectively, and since no compensatory changes of the polyamine synthetic enzymes, were induced by inhibition of polyamine oxidase, the rate of acetyl-polyamine accumulation is assumed to be a measure for polyamine turnover. The decrease of brain putrescine levels by 70 percent in the brains of MDL 72527-treated animals suggests the quantitative significance of putrescine reutilisation. Pretreatment of the animals with D, L-agr-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase reduced both, polyamine turnover rate and the extent of putrescine reutilization. Inhibition of GAPA-T produced a significant increase of polyamine turnover in brain, in agreement with the known induction of ornithine decarboxylase activity after treatment with inhibitors of GABA-T.
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