Glucocorticoids increase Ca2+ uptake and [3H]dihydropyridine binding in A7r5 vascular smooth muscle cells.
Increased levels of corticosteroids result in the development of hypertension in vivo. To investigate whether corticosteroids modulate calcium handling in vascular smooth muscle cells, we studied 45Ca2+ uptake and binding of [methyl-3H]PN 200-110, a potent dihydropyridine Ca2+ antagonist, in A7r5 vascular smooth muscle cells. Forty-eight-hour treatment with 100 nM dexamethasone increased the unidirectional 45Ca2+ uptake during a 2-min period, and the 30-min 45Ca2+ uptake of dexamethasone-treated cells was 95% greater than that of nontreated cells. The lag time for the dexamethasone effect on Ca2+ uptake was approximately 8 h. The effect of dexamethasone was blocked by the glucocorticoid antagonist RU 38486, whereas it was not affected by the mineralocorticoid antagonist RU 26752. After cessation of the dexamethasone treatment, 45Ca2+ uptake returned to the control level by 24 h. The effect of dexamethasone was completely blocked by nifedipine in a dose-dependent manner. Scatchard plots of [methyl-3H]PN 200-110 binding revealed two binding sites (Kd; 0.02 and 1 nM), and dexamethasone increased the number of the higher affinity binding sites. These results indicate that glucocorticoids increase Ca2+ uptake possibly mediated by an increase in the number of dihydropyridine-sensitive Ca2+ channels.
Hayashi
T
T
Third Department of Internal Medicine, Fukui Medical School, Japan.
Nakai
T
T
Miyabo
S
S
D000584:Amiloride; D000704:Analysis of Variance; D000732:Androstanols; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D002452:Cell Count; D002460:Cell Line; D003513:Cycloheximide; D003609:Dactinomycin; D003907:Dexamethasone; D004095:Dihydropyridines / Q000378:metabolism*; D004553:Electric Conductivity; D005938:Glucocorticoids / Q000378:metabolism / Q000502:physiology*; D007213:Indomethacin; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives; D014867:Water / Q000378:metabolism
D000732:Androstanols; D015220:Calcium Channels; D004095:Dihydropyridines; D005938:Glucocorticoids; D011506:Proteins; D011965:Receptors, Glucocorticoid; D014867:Water; D003609:Dactinomycin; D013148:Spironolactone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; C047175:7-propyl spirolactone; D000584:Amiloride; C038806:1,4-dihydropyridine; D003907:Dexamethasone; D003513:Cycloheximide; D011188:Potassium; D002118:Calcium; D007213:Indomethacin