Effects of ginsenosides on carbachol-stimulated formation of inositol phosphates in rat cortical cell cultures

We examined the effect of ginseng total saponins (GTS) on phosphoinositide metabolism stimulated by activation of muscarinic receptor using rat cortical cultures. Carbachol stimulated formation of [H-3]inositol phosphates ([H-3]InsPs) by 3.3-fold over basal level in [H-3]inositol-prelabeled cells. Pretreatment of GTS inhibited formation of [H-3]InsPs evoked by carbachol by 70%-90%. Addition of GTS alone had no effect on the basal formation of [H-3]InsPs. The inhibitory effect of the GTS on carbachol-stimulated formation of [H-3]InsPs was dose-and time-dependent. IC50 was 6.0 +/- 2.8 mug/ml. We also examined the effect of GTS on [H-3]InsP(1), [H-3]InsP(2), or [H-3]InsP(3) formation evoked by carbachol. Although GTS had no effect on the basal [H-3]InsP(1), [H-3]InsP(2), or [H-3]InsP(3) formation, pretreatment of GTS inhibited [H-3]InsP(1), [H-3]InsP(2), or [H-3]InsP(3) formation evoked by carbachol, respectively. Addition of individual ginsenosides such as ginsenoside Rb-1, Rc, Rd, Re, or Rg(2) had no effect on the basal formation of [H-3]InsPs, whereas pretreatment of ginsenoside Rb-2, Rc, Rd, Re, Rf, Rg(1) or Rg(2) inhibited formation of [H-3]InsPs evoked by carbachol by 79%-89%. The results suggest that the inhibitory effect of GTS and its individual ginsenosides on carbachol-stimulated formation of [H-3]InsPs in cortical neurons could be one pharmacological action of Panax ginseng.