title: Glucocorticoids increase Ca2+ uptake and [3H]dihydropyridine binding in A7r5 vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Fukui Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Nakai
authors.forename: S
authors.initials: S
authors.lastname: Miyabo
mesh_terms: 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
chemical_list: 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