MDR1/P-glycoprotein function. I. Effect of hypotonicity and inhibitors on rhodamine 123 exclusion

James L. Weaver, Leslie McKinney, Patricia V. Schoenlein, Sarah Goldenberg, Michael M. Gottesman, Adorjan Aszalos

Research output: Contribution to journalArticlepeer-review


The MDR1 protein (P-glycoprotein) is a membrane ATPase whose expression results in resistance to several anti-tumor drugs. It has been proposed that the MDR1 protein, in addition to its pumplike properties, can function as (Gill et al. Cell 71: 23-32, 1992; Altenberg et al. Cancer Res. 54: 618-622, 1994) or mediate the activity of (Hardy et al. EMBO J. 14: 68-75, 1995) a hypotonic stress-induced Cl- current. In addition, one study found that drug transport and Cl- channel-associated functions of MDR1 were separable and mutually exclusive and that, when cells were swelled, the MDR1 protein could not transport substrate. This hypothesis was tested in four pairs of isogenic cell lines with MDR1 transfectants expressing 8,000-55,000 MDR1 antibody binding sites per cell. Cytoplasmic exclusion of rhodamine 123 was used as an indicator of MDR1 function to measure the effect of hypotonic stress, MDR1 inhibitors, and Cl- channel blockers on MDR1 transport function. It was found that MDR1 activity and its inhibition by cyclosporine A or flufenamic acid were unaffected by hypotonicity alone or in combination with Cl- channel blockers.

Original languageEnglish (US)
Pages (from-to)C1447-C1452
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 39-5
StatePublished - May 1996


  • 4,4'- diisothiocyanostilbene-2,2'-disulfonic acid
  • 4- acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid
  • chloride channel
  • cyclosporine A
  • drug efflux
  • flufenamic acid
  • multidrug resistance

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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