Endothelin-1 stimulates c-fos mRNA expression in C6 glioma cells via MAP kinase pathway

Abstract

Exposure of C6 glioma cells to endothelin-1 (ET-1) caused dose-dependent (10 −11 M to 10 −7 M) increments in intracellular calcium concentration ([Ca 2+] i) and c-fos mRNA expression (4.5-fold) that were abolished by the endothelin A receptor antagonist, BQ610, and by inhibition of phospholipase C with U73122. ET-1 stimulated c-fos mRNA expression was also inhibited by protein kinase C inhibition (chelerythrine) and by the MAP kinase kinase inhibitor PD98059, but not by inhibitors of tyrosine kinases, protein kinase A type I or II, calmodulin kinase II, or calcium channel blockade. C6 cells treated with ET-1 demonstrated a significant increase in MAP kinase activity as evidenced by Western blotting. These results indicate a mechanism of long-term signaling by ET-1 involving an ET A receptor-mediated, phospholipase C β-linked pathway that is dependent on protein kinase C and MAP kinase activation.