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.
Carfagna
N
N
CNS Biology, Pharmacia and Upjohn, Milan, Italy. nicola.carfagna@itner.pharmacia.se
Cavanus
S
S
Damiani
D
D
Salmoiraghi
P
P
Fariello
R
R
Post
C
C
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002217:Carbachol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009530:Nicergoline / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018697:Nootropic Agents; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D009530:Nicergoline; D009638:Norepinephrine