Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells.
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), PSC-833, 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.
Bello-Reuss
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E
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA.
Ernest
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S
Holland
O B
OB
Hellmich
M R
MR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D001943:Breast Neoplasms; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D018432:Drug Resistance, Multiple / Q000235:genetics; D005047:Etoposide / Q000633:toxicity; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020319:Oligodeoxyribonucleotides, Antisense; D020112:Rhodamine 123; D000450:Aldosterone; D005047:Etoposide