Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells
| Autor: | Sylvain Ernest, Elsa Bello-Reuss, O. Bryan Holland, Mark R. Hellmich |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
endocrine system diseases Transcription Genetic Physiology medicine.drug_class Breast Neoplasms Transfection Cell Line Oligodeoxyribonucleotides Antisense chemistry.chemical_compound Cyclosporin a Internal medicine Adrenal Glands polycyclic compounds medicine Tumor Cells Cultured Humans Rhodamine 123 ATP Binding Cassette Transporter Subfamily B Member 1 Aldosterone P-glycoprotein Etoposide integumentary system biology Reverse Transcriptase Polymerase Chain Reaction Cell Membrane Cell Biology Molecular biology Drug Resistance Multiple Glomerular Mesangium medicine.anatomical_structure Endocrinology chemistry Cell culture Zona glomerulosa Mineralocorticoid biology.protein Female Efflux |
| Zdroj: | American journal of physiology. Cell physiology. 278(6) |
| ISSN: | 0363-6143 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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