Calcium-mediated endothelin signaling in C6 rat glioma cells

Endothelin induced intracellular Ca2+ signaling was studied in C6 rat glial cells. Endothelins 1 and 3 increased transiently intracellular Ca2+ concen tration, endothelin 3 being less potent inducer. Dibutyryl-cAMP treated cel ls responded with less sensitivity. While BQ123, a specific endothelin A re ceptor antagonist, inhibited both endothelins induced response in prolifera ting cells, it failed to inhibit in dibutyryl-cAMP treated ones. IRL1620, a specific endothelin B receptor agonist, was devoid of any significant effe ct. Although re-stimulation by both endothelins after endothelin-l did not cause any Ca2+ oscillation, both endothelins evoked new Ca2+ transient afte r endothelin-3 stimulation. Our findings suggest that endothelin induced Ca 2+ signaling is mediated probably through the receptor A in proliferating C 6 cells. The lack of both BQ123 and IRL 1620 effect in dibutyryl-cAMP treat ed cells could be caused by an alteration of endothelin A receptor alone, b y a change of receptor expression pattern, or by more complex postreceptor mechanism.