Functional analysis of CFTR chloride channel activity in cells with elevated MDR1 expression

Lishuang Cao, Grzegorz Owsianik, Martine Jaspers, Annelies Janssens, Harry Cuppens, Jean Jacques Cassiman, Bernd Nilius

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Using the patch-clamp method, we investigated a relationship between MDR1 expression and its effects on the CFTR channel function. Incubation of CaCo-2 cells with increasing concentrations of doxorubicin resulted in a reduction of CFTR chloride channel activity in a dose-dependent manner. This reduction was associated with a decrease of CFTR mRNA and simultaneous up-regulation of MDR1 mRNA in the presence of doxorubicin. Similar alteration of the CFTR function was observed in CaCo-2 cells transiently overexpressing MDR1. No alterations of the cAMP-dependent chloride currents were observed in COS-1 cells transiently co-expressing CFTR and MDR1 from strong CMV promoters. This indicated that repression of CFTR by MDR1 induction requires the presence of the native CFTR promoter. © 2003 Elsevier Science (USA). All rights reserved.
    Original languageEnglish
    Pages (from-to)248-252
    Number of pages4
    JournalBiochemical and Biophysical Research Communications
    Volume304
    Issue number2
    DOIs
    Publication statusPublished - 2 May 2003

    Keywords

    • cAMP-activated chloride channel
    • CFTR
    • Co-expression
    • Cystic fibrosis
    • Doxorubicin
    • MDR1
    • Multidrug resistance
    • Patch-clamp technique

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