Modulation of phosphoinositide turnover by chronic nicergoline in rat brain

Basal and agonist-stimulated phosphoinositide (PI) turnover and inositol 1,4,5 -trisphospate (InsP3) content in rat brain were investigated after chronic nicergoline (SERMION) treatment. Oral administration of nicergoline (5 mg/kg b.i.d. for 7 weeks) enhanced the basal turnover of PI in the cerebral cortex compared to controls. This effect was paralleled by a significant rise of cortical InsP3 levels. No significant changes of noradrenaline- or carbachol-induced accumulation of [3H]-inositol-I-phophate ([3H]-InsP1) were found in cortices from nicergoline-treated rats. On the contrary, in the striatum nicergoline significantly potentiated the responsiveness of noradrenaline- and carbachol-stimulated PI turnover, leaving unchanged the basal production of [3H]-InsP1 and InsP3 levels. The results suggest that the interaction of nicergoline with PI transducing pathway might have relevance to the mechanisms of action of nicergoline.