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 45Ca2+ uptake and dihydropyridine binding by rat A7r5 cells. FR139317 inhibited the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]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 dihydropyridine-sensitive channels in an autocrine manner, possibly linked to the activation of protein kinase C-alpha.
Kato
H
H
Third Department of Internal Medicine, Fukui Medical School, Japan.
Hayashi
T
T
Koshino
Y
Y
Oida
K
K
Kutsumi
Y
Y
Nakai
T
T
Miyabo
S
S
D000818:Animals; D001011:Aorta; D001381:Azepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004095:Dihydropyridines / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000096:biosynthesis*; D007211:Indoles / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017466:Receptors, Endothelin / Q000502:physiology*
D001381:Azepines; D002250:Carbon Radioisotopes; D004095:Dihydropyridines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D017466:Receptors, Endothelin; C079574:FR 139317; C038806:1,4-dihydropyridine; D003907:Dexamethasone; D002118:Calcium; D017275:Isradipine