Cerebral Polyamine Metabolism: Inhibition of Spermidine Biosynthesis by Dicyclohexylamine

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Abstract
Since a specific inhibition of cerebral spermidine (Spd) synthase activity by alicyclic amines was preliminarily observed in vitro, the in vivo inhibitory effectiveness of dicyclohexylamine (DCHA) on Spd biosynthesis in 21-day-old rat brain was examined. A previously reported HPLC [high performance liquid chromatography] procedure was modified to analyze the cerebral levels of DCHA at the time of polyamine determinations. The i.p. injected DCHA crossed the blood-brain barrier easily, reaching high levels in the cerebral tissue (.apprx. 750 nmol/g brain) within 1 h of its administration. The effect of the drug on the polyamine metabolism resulted in a significant depletion of Spd biosynthesis from the 6th h after the treatment and in an earlier and prolonged increase of the putrescine (Pt) steady-state levels. The spermine (Spm) endogenous pools remained unchanged throughout the 24-h post-DCHA period. Following the intracerebral administration of [1,4-14C]Pt, significantly lower specific radioactivity (SRA) values for labeled Pt and Spd were recorded in the brains of DCHA-treated animals. After intracerebral [14C]Spd injection, the SRA of newly formed [14C]Spm remained unchanged, confirming the specificity of the DCHA effect on the Spd biosynthesis.