Regulation of sodium-calcium exchanger by glucocorticoids and growth factors in vascular smooth muscle.
The findings presented in this paper indicate that glucocorticoids down-regulate Na(+)-Ca2+ exchanger (NCX) mRNA and activity in aortic myocytes. Serum and purified growth factors reversed NCX down-regulation. Dexamethasone, cortisol, or aldosterone decreased NCX activity by approximately 55% in 24 h. Dexamethasone was > 100 times more potent than aldosterone, indicating that a glucocorticoid receptor mediates the down-regulation of NCX activity. Dexamethasone decreased the NCX transcript to approximately 10% of the control level in 24 h without affecting plasma membrane Ca(2+)-ATPase transcripts. Fetal bovine serum increased NCX mRNA 10-fold in 4 h in dexamethasone-treated cells and restored full NCX activity in 16 h. The increase in NCX mRNA produced by serum required RNA and protein synthesis. Thrombin moderately increased NCX mRNA and partially restored NCX activity in dexamethasone-treated cells. Insulin, platelet-derived growth factor, or epidermal growth factor increased NCX mRNA similarly to thrombin. Tunicamycin, which inhibits N-linked glycosylation, prevented the restoration of NCX activity. These observations suggest that changes in the level of NCX mRNA mediate the opposing influences of glucocorticoids and growth factors on NCX activity. NCX induction by growth stimuli would increase the capacity for Ca2+ efflux and cycling between the cell and the environment.
Department of Pharmacology, School of Medicine, University of Alabama at Birmingham 35294.
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D013917:Thrombin / Q000494:pharmacology
D002352:Carrier Proteins; D005938:Glucocorticoids; D006133:Growth Substances; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D012964:Sodium; D013917:Thrombin; D011188:Potassium; D002118:Calcium; D006854:Hydrocortisone