Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells

Elsa Bello-Reuss, Sylvain Ernest, Owen B Holland, Mark R. Hellmich

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

We determined the role of the multidrug resistance (MDR1) gene product, P-glycoprotein (PGP), in the secretion of aldosterone by the adrenal cell line NCI-H295. Aldosterone secretion is significantly decreased by the PGP inhibitors verapamil, cyclosporin A (CSA), PSC833, and vinblastine. Aldosterone inhibits the efflux of the PGP substrate rhodamine 123 from NCI- H295 cells and from human mesangial cells (expressing PGP). CSA, verapamil, and the monoclonal antibody UIC2 significantly 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 and no PGP), the efflux of microinjected FL-aldosterone was slow. In BC19/3 cells (MCF7 cells transfected with MDR1), the efflux of FL-aldosterone was rapid and it was inhibited by verapamil, indicating that transfection with MDR1 cDNA confers the ability to transport FL-aldosterone. These results strongly indicate that PGP plays a role in the secretion of aldosterone by NCI-H295 cells and in other cells expressing MDR1, including normal adrenal cells.

Original languageEnglish (US)
Pages (from-to)C1256-C1265
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number6 47-6
DOIs
StatePublished - Jan 1 2000

Keywords

  • MDR1
  • Multidrug resistance
  • P-glycoprotein
  • Transport
  • Zona glomerulosa

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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