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

We determined whether endothelin-1 (ET-1) is associated with glucocort icoid-induced Ca2+ influx into vascular smooth muscle cells by examini ng the effects of the ETA receptor antagonist FR139317 on dexamethason e-induced Ca-45(2+) uptake and dihydropyridine binding by rat A7r5 cel ls. FR139317 inhibited the dexamethasone-induced Ca-45(2+) uptake and [methyl-H-3]PN 200-110 binding in a dose-dependent manner. Slot blot a nalysis revealed that dexamethasone increased protein kinase C-alpha i n A7r5 cells and that this effect was also abolished by FR139317. Dexa methasone stimulated the release of immunoreactive endothelin-1 from A 7r5 cells into the culture medium. These results suggest that endothel in participates in the glucocorticoid-induced Ca2+ influx through dihp dropyridine-sensitive channels in an autocrine manner, possibly linked to the activation of protein kinase C-alpha. (C) Press Academic Press , Inc.