Glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels linked to activation of protein kinase C in vascular smooth muscle cells.
To clarify whether protein kinase is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells, we investigated the effects of protein kinase inhibitors on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding in A7r5 cells. Protein kinase C inhibitors (staurosporine and UCN-01) abolished the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding. In contrast, KT5720 and KT5823, which are more specific inhibitors of cAMP-dependent protein kinase and cGMP-dependent protein kinase, respectively, did not affect the effects of dexamethasone. Treatment with 100 nM dexamethasone for 48 hours increased protein kinase C activity in A7r5 cells. These results suggest that glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels, linked to activation of protein kinase C in vascular smooth muscle cells.
Kato
H
H
Third Department of Internal Medicine, Fukui Medical School, Japan.
Hayashi
T
T
Koshino
Y
Y
Kutsumi
Y
Y
Nakai
T
T
Miyabo
S
S
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002227:Carbazoles; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D019311:Staurosporine / Q000031:analogs & derivatives
D000470:Alkaloids; D015220:Calcium Channels; D002227:Carbazoles; D007211:Indoles; D011758:Pyrroles; C073601:KT 5823; C057416:KT 5720; C054852:7-hydroxystaurosporine; D003907:Dexamethasone; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium; D017275:Isradipine