MODULATION OF PHOSPHOINOSITIDE TURNOVER BY CHRONIC NICERGOLINE IN RAT-BRAIN

Basal and agonist-stimulated phosphoinositide (PI) turnover and inosit ol 1,4,5 -trisphospate (InsP(3)) content in rat brain were investigate d after chronic nicergoline (SERMION(R)) treatment. Oral administratio n of nicergoline (5 mg/kg b.i.d. for 7 weeks) enhanced the basal turno ver of PI in the cerebral cortex compared to controls. This effect was paralleled by a significant rise of cortical InsP(3) levels. No signi ficant changes of noradrenaline- or carbachol-induced accumulation of [H-3]-inositol-1-phophate ([H-3]-InsP(1)) were found in cortices from nicergoline-treated rats. On the contrary, in the striatum nicergoline significantly potentiated the responsiveness of noradrenaline- and ca rbachol-stimulated PI turnover, leaving unchanged the basal production of [H-3]-InsP(1) and InsP(3) levels. The results sug gest that the in teraction of nicergoline with PI transducing pathway might have releva nce to the mechanisms of action of nicergoline.