Biphasic modulation of intracellular Ca2+ concentration by interleukin-1β in cortical synaptosomes:: involvement of a pertussis toxin-sensitive G-protein and mitogen-activated protein kinase

THE modulation of intracellular Ca2+ concentration ([Ca2+](i)) by the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) was assessed in synaptosomes loaded with the Ca2+-sensitive dye, Fura-2AM. IL-1 beta was found to exert a biphasic effect on the KCl-induced rise in [Ca2+](i), extending an inhibitory effect at lower (3.5 ng/ml) concentrations, and a stimulatory effect at high (100 ng/ml) concentrations. The inhibitory action of IL-1 beta on [Ca2+](i) was sensitive to pertussis toxin (PTX; 2 mu g/ml), indicating a role for a PTX-sensitive G-protein, but was unaffected by the p42 mitogen-activated protein kinase kinase (MAP kinase kinase) inhibitor, PD 098059 (2 mu M). In contrast, the stimulatory action of higher concentrations of IL-1 beta on [Ca2+](i) was blocked by PD 098059 and unaffected by PTX. We conclude that the biphasic actions of IL-1 beta on the KCl-induced rise in [Ca2+](i) are mediated through activation of alternative second messenger pathways. (C) 1998 Rapid Science Ltd.