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

We have investigated the effects of interleukin (IL)-1 beta 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-1 beta (10(3) U/mL) and LPS (1 mu g/mL) for 24 h significantly inhibited 100 nM ET-1-induced increase in intracellular Ca2+ either in the presence or absence of external Ca2+. Their inhibitory effects were in dose-dependent (IL-1 beta; 50-1000 U/mL, LPS; 10-1000 ng/mL) and time-dependent (12-24 h) manners. A tyrosine kinase antagonist genistein (50 mu M) but not a protein kinase C inhibitor H7 (30 mu M) prevented the inhibition of the ET response by IL-1 beta 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-1 beta and LPS.