As previously reported (Morita, M. et al, 2001 SFN abstract), Ca2+ response to neurotransmitters, such as glutamate and ATP of rat cortical type I astrocyte in culture is switched from transient to oscillatory by the treatment with growth factors (GFs), EGF and bFGF for several days, and pro-inflammatory cytokines, such as IL1β and TNFα and LPS cancel it. To elucidate the signal transduction pathway invoved, we examined the effect of kinase inhibitors. ERK MAP kinase cascade inhibitor, U0126 blocked the Ca2+ oscillation, but PD95098 and PI3 kinase inhibitors were not effective. This means that ERK MAP kinase cascade is essential for the switching and that both of MEK 1 and 2 are involved. This cascade was further investigated with anti-phospho-ERK antibody and zif268 promoter, which is an immediate early gene activated by ERK. The response of zif268 promoter to GFs was inhibited by both of U0126 and cytokine, but cytokine failed to inhibit the GFs induced phosphorylation of ERK. This indicates that cytokin...