Biphasic modulation of intracellular Ca2+ concentration by interleukin-1beta 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-1beta (IL-1beta) was assessed in synaptosomes loaded with the Ca2+-sensitive dye, Fura-2AM. IL-1beta 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-1beta on [Ca2+]i was sensitive to pertussis toxin (PTX; 2 microg/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 microM). In contrast, the stimulatory action of higher concentrations of IL-1beta on [Ca2+]i was blocked by PD 098059 and unaffected by PTX. We conclude that the biphasic actions of IL-1beta on the KCl-induced rise in [Ca2+]i are mediated through activation of alternative second messenger pathways.
Campbell
V
V
Department of Physiology, Trinity College, Dublin, Ireland.
Lynch
M A
MA
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007375:Interleukin-1; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium