Modulation of endothelin-induced intracellular Ca²⁺ mobilization by interleukin-1β and lipopolysaccharide in C6 rat glioma cells

We have investigated the effects of interleukin (IL)-(IL)-1̄ and lipopolysaccharide (LPS) on endothelin (ET)-induced intracellular Ca²⁺ rise in C6 rat glioma cells in order to study the mechanisms of their effects on Ca²⁺ signaling systems. Pretreatment with IL-1̄ (10³ U/mL) and LPS (1 μg/mL) for 24 h significantly inhibited 100 nM ET-l-induced increase in intracellular Ca²⁺ either in the presence or absence of external Ca²⁺. Their inhibitory effects were in dose-dependent (IL-1β; 50-1000 U/mL, LPS; 10-1000 ng/mL) and time-dependent (12-24 h) manners. A tyrosine kinase antagonist genistein (50 μM) but not a protein kinase C inhibitor H7 (30 μM) prevented the inhibition of the ET response by IL-1β and LPS. These results suggest that activation of tyrosine kinase may be essential for the inhibition of the ET receptor-mediated Ca²⁺ signaling systems by IL-1β and LPS.