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| The multidrug resistance P-glycoprotein modulates cell regulatory volume decrease |
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| Author(s): Valverde MA, Bond TD, Hardy SP, Taylor JC, Higgins CF, Altamirano J, AlvarezLeefmans FJ |
| Source: EMBO JOURNAL Volume: 15 Issue: 17 Pages: 4460-4468 Published: SEP 2 1996 |
| Times Cited: 82 References: 42 |
| Abstract: Cell volume is frequently down-regulated by the activation of anion channels, The role of cell swelling-activated chloride channels in cell volume regulation has been studied using the patch-clamp technique and a non-invasive microspectrofluorimetric assay for changes in cell volume, The rate of activation of these chloride channels was shown regulatory volume decrease hyposmotic solutions, Expression of the human MDR1 or mouse mdr1a genes, but not the mouse mdr1b gene, encoding the multidrug resistance P-glycoprotein (P-gp), increased the rate of channel activation and the rate of RVD, In addition, P-gp decreased the magnitude of hyposmotic shock required to activate the channels and to elicit RVD, Tamoxifen selectively inhibited both chloride channel activity and RVD, No effect on potassium channel activity was elicited by expression of P-gp, The data show that, in these cell types, swelling-activated chloride channels have a central role in RVD, Moreover, they clarify the role of P-gp in channel activation and provide direct evidence that P-gp, through its effect on chloride channel activation, enhances the ability of cells to down-regulate their volume. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV OXFORD, JOHN RADCLIFFE HOSP, NUFFIELD DEPT CLIN BIOCHEM, OXFORD OX3 9DU, ENGLAND
2. UNIV OXFORD, JOHN RADCLIFFE HOSP, IMPERIAL CANC RES FUND LABS, INST MOL MED, OXFORD OX3 9DU, ENGLAND
3. UNIV LONDON KINGS COLL, DEPT PHYSIOL, LONDON WC2R 2LS, ENGLAND
4. INST MEXICANO PSIQUIATRIA, DEPT NEUROBIOL, MEXICO CITY 14370, DF MEXICO
5. INST POLITECN NACL, CTR INVEST & ESTUDIOS AVANZADOS, MEXICO CITY 07000, DF MEXICO
6. UNIV TEXAS, MED BRANCH, DEPT PHYSIOL & BIOPHYS, GALVESTON, TX 77555 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: VH004 |
| ISSN: 0261-4189 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |