| Comparison of furosemide and vinblastine secretion from cell lines overexpressing multidrug resistance protein (P-glycoprotein) and multidrug resistance-associated proteins (MRP1 and MRP2). | |
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MedLine Citation:
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PMID: 11834888 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent studies in our laboratory have shown that the loop diuretic, furosemide, is actively secreted by Caco-2 cells and rat jejunal tissue. This active secretion could be the result of efflux transporters such as P-gp, MRP1 or MRP2 (cMOAT). To determine if any of these transporters is responsible for the secretion of furosemide, we compared directional permeability in the wild-type cell lines, MDCK strains I and II, and LLC-PK1, vs. cell lines that overexpress a single transporter, in both the presence and absence of various inhibitors, for furosemide as compared to vinblastine. Sulfinpyrazone significantly inhibited the transport of vinblastine in MRP2 expressing cells, but not the wild-type controls. Vinblastine could not be confirmed as a substrate of MRP1. We were also unable to demonstrate that any particular transporter affected furosemide in excess of the background effects of endogenous transporters in the parental cell lines. Furosemide secretion from these kidney-derived cell lines is probably not the primary result of any of the well characterized efflux transporters (P-gp, MRP1 or MRP2), although they may still play a role in the observed Caco-2 secretion. This equivocal result acknowledges the difficulty in trying to determine the effect of a single protein in a complicated expression system. |
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Authors:
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Shawn D Flanagan; Carolyn L Cummins; Miki Susanto; Xiaoli Liu; Lori H Takahashi; Leslie Z Benet |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Pharmacology Volume: 64 ISSN: 0031-7012 ISO Abbreviation: Pharmacology Publication Date: 2002 |
Date Detail:
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Created Date: 2002-02-08 Completed Date: 2002-05-14 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0152016 Medline TA: Pharmacology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 126-34 Citation Subset: IM |
Copyright Information:
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Copyright 2002 S. Karger AG, Basel |
Affiliation:
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Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, Calif. 94143-0446, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents, Phytogenic / metabolism* Biological Transport / drug effects Blotting, Western Cell Line Cell Membrane Permeability / drug effects Cyclosporine / pharmacology Diuretics / metabolism* Dogs Drug Resistance, Multiple Furosemide / metabolism* Kidney / cytology Membrane Transport Proteins* Multidrug Resistance-Associated Proteins / biosynthesis* P-Glycoprotein / biosynthesis* Sulfinpyrazone / pharmacology Transfection Vinblastine / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GM07175/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Diuretics; 0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/multidrug resistance-associated protein 1; 0/multidrug resistance-associated protein 2; 54-31-9/Furosemide; 57-96-5/Sulfinpyrazone; 59865-13-3/Cyclosporine; 865-21-4/Vinblastine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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