Cerebral polyamine metabolism: inhibition of spermidine biosynthesis by dicyclohexylamine.

Abstract

Since a specific inhibition of cerebral spermidine (Spd) synthase activity by alicyclic amines was preliminarily observed in vitro, we examined the in vivo inhibitory effectiveness of dicyclohexylamine (DCHA) on Spd biosynthesis in 21-day-old rat brain. For this purpose a previously reported HPLC procedure (Porta et al., 1981a) was modified to analyze the cerebral levels of DCHA at the time of polyamine determinations. The intraperitoneally injected DCHA was shown to cross the blood-brain barrier easily, reaching high levels in the cerebral tissue (approximately 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 sixth hour after the treatment and in an earlier and prolonged increase of the putrescine (Pt) steady-state levels. Conversely, the spermine (Spm) endogenous pools remained unchanged throughout the 24-h post-DCHA period. Moreover, following the intracerebral administration of [1,4-14C]Pt, significantly lower specific radioactivity (s.r.a.) values for labeled Pt and Spd were recorded in the brains of DCHA-treated animals. Conversely, after intracerebral [14C]Spd injection, the s.r.a. of newly formed [14C]Spm remained unchanged, confirming the specificity of the DCHA effect on the Spd biosynthesis.