P-glycoprotein expression and the regulation of [Ca2+]i during cell swelling

D. L. Bovell, H. L. McAlroy, S. M. Wilson, J. A. Plumb, P. Thompson

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Abstract

Hypotonic solutions increase [Ca2+]i in P-gp-expressing adenocarcinoma cells selected for adrimaycin resistance (A2780.ad), but not in this strain's parental line (A2780.wt) (Bovell and Wilson, J. Physiol. 489: 135P-136P, 1996). To explore the possibility that this reflects differential expression of P-gp, we established a revertant strain (A2780.rev) that contained fewer cells in which P-gp could be detected by cytochemistry (A2780.wt: 0%, A2780.ad: 93 ± 5%. A2780.rev: 34 ± 7%). This strain was also more sensitive to adriamycin (IC50 values: A2780.wt: 0.001 ± 0.0003 μM, A2780.ad: 5.6 ± 0.7 μM, A2780.rev: 0.6 ± 0.4 μM) and exported rhodamine-123, a fluorescent P-gp substrate, at a reduced rate (half times: A2780.wt: > 5 h, A2780.ad: 5.5 ± 0.8 min, A2780.rev, 116 ± 27 min). Cell swelling increased [Ca2+]i in A2780.ad cells (rise in Fura-2 ratio: 0.36 ± 0.09) but evoked a smaller response in the A2780.rev cells (0.12 ± 0.03) whilst the A2780.wt cells were unresponsive. However, 0.1 μM ionomycin evoked similar responses in each stain (A2780.wt: 1.5 ± 0.24, A2780.ad: 1.0 ± 0.11, A2780.rev: 1.2 ± 0.15).

Original languageEnglish
Pages (from-to)A1022
JournalFASEB Journal
Volume12
Issue number5
Publication statusPublished - 20 Mar 1998

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Bovell, D. L., McAlroy, H. L., Wilson, S. M., Plumb, J. A., & Thompson, P. (1998). P-glycoprotein expression and the regulation of [Ca2+]i during cell swelling. FASEB Journal, 12(5), A1022.