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Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells 总被引:2,自引:0,他引:2
Bello-Reuss E Ernest S Holland OB Hellmich MR 《American journal of physiology. Cell physiology》2000,278(6):C1256-C1265
We determinedthe role of the multidrug resistance (MDR1) gene product,P-glycoprotein (PGP), in the secretion of aldosterone by the adrenalcell line NCI-H295. Aldosterone secretion is significantly decreased bythe PGP inhibitors verapamil, cyclosporin A (CSA), PSC-833, andvinblastine. Aldosterone inhibits the efflux of the PGP substraterhodamine 123 from NCI-H295 cells and from human mesangial cells(expressing PGP). CSA, verapamil, and the monoclonal antibody UIC2significantly decreased the efflux of fluorescein-labeled (FL)-aldosterone microinjected into NCI-H295 cells. In MCF-7/VP cells,expressing multidrug resistance-associated protein (MRP) but not PGP,and in the parental cell line MCF7 (expressing no MRP andno PGP), the efflux of microinjected FL-aldosterone was slow. In BC19/3cells (MCF7 cells transfected with MDR1), the efflux of FL-aldosteronewas rapid and it was inhibited by verapamil, indicating thattransfection with MDR1 cDNA confers the ability to transportFL-aldosterone. These results strongly indicate that PGP plays a rolein the secretion of aldosterone by NCI-H295 cells and in other cellsexpressing MDR1, including normal adrenal cells. 相似文献
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