BIPHASIC MODULATION OF INTRACELLULAR CA2-1-BETA IN CORTICAL SYNAPTOSOMES - INVOLVEMENT OF A PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN AND MITOGEN-ACTIVATED PROTEIN-KINASE( CONCENTRATION BY INTERLEUKIN)

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 bet a 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) concentrati ons, 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-prote in, but was unaffected by the p42 mitogen-activated protein kinase kin ase (MAP kinase kinase) inhibitor, PD 098059 (2 mu M). In contrast, th e 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) ar e mediated through activation of alternative second messenger pathways . (C) 1998 Rapid Science Ltd.