AUTOCRINE PRODUCTION OF ENDOTHELIN-1 PARTICIPATES IN THE GLUCOCORTICOID-INDUCED CA2+ INFLUX INTO VASCULAR SMOOTH-MUSCLE CELLS

We determined whether endothelin-1 (ET-1) is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells by examining the effects of the ETA receptor antagonist FR139317 on dexamethasone-induced Ca-45(2+) uptake and dihydropyridine binding by rat A7r5 cells. FR139317 inhibited the dexamethasone-induced Ca-45(2+) uptake and [methyl-H-3]PN 200-110 binding in a dose-dependent manner. Slot blot analysis revealed that dexamethasone increased protein kinase C-alpha in A7r5 cells and that this effect was also abolished by FR139317. Dexamethasone stimulated the release of immunoreactive endothelin-1 from A7r5 cells into the culture medium. These results suggest that endothelin participates in the glucocorticoid-induced Ca2+ influx through dihpdropyridine-sensitive channels in an autocrine manner, possibly linked to the activation of protein kinase C-alpha. (C) Press Academic Press, Inc.