Calcium-mediated endothelin signaling in C6 rat glioma cells

Endothelin induced intracellular Ca(2+)signaling was studied in C6 rat glial cells. Endothelins 1 and 3 increased transiently intracellular Ca(2+)concentration, endothelin 3 being less potent inducer. Dibutyryl-cAMP treated cells responded with less sensitivity. While BQ123, a specific endothelin A receptor antagonist, inhibited both endothelins induced response in proliferating cells, it failed to inhibit in dibutyryl-cAMP treated ones. IRL1620, a specific endothelin B receptor agonist, was devoid of any significant effect. Although re-stimulation by both endothelins after endothelin-1 did not cause any Ca(2+)oscillation, both endothelins evoked new Ca(2+)transient after endothelin-3 stimulation. Our findings suggest that endothelin induced Ca(2+)signaling is mediated probably through the receptor A in proliferating C6 cells. The lack of both BQ123 and IRL 1620 effect in dibutyryl-cAMP treated cells could be caused by an alteration of endothelin A receptor alone, by a change of receptor expression pattern, or by more complex postreceptor mechanism.