Cystic Fibrosis Transmembrane Conductance Regulator Facilitates ATP Release by Stimulating a Separate ATP Release Channel for Autocrine Control of Cell Volume Regulation

Gavin M. Braunstein, Richard M. Roman, John P. Clancy, Brian A. Kudlow, Amanda L. Taylor, Vadim Gh Shylonsky, Biljana Jovov, Krisztina Peter, Tamas Jilling, Iskander I. Ismailov, Dale J. Benos, Lisa M. Schwiebert, J. Greg Fitz, Erik M. Schwiebert

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

These studies provide evidence that cystic fibrosis transmembrane conductance regulator (CFTR) potentiates and accelerates regulatory volume decrease (RVD) following hypotonic challenge by an autocrine mechanism involving ATP release and signaling. In wild-type CFTR-expressing cells, CFTR augments constitutive ATP release and enhances ATP release stimulated by hypotonic challenge. CFTR itself does not appear to conduct ATP. Instead, ATP is released by a separate channel, whose activity is potentiated by CFTR. Blockade of ATP release by ion channel blocking drugs, gadolinium chloride (Gd3+) and 4,4′-diisothiocyanatostilbene-2,2′disulfonic acid (DIDS), attenuated the effects of CFTR on acceleration and potentiation of RVD. These results support a key role for extracellular ATP and autocrine and paracrine purinergic signaling in the regulation of membrane ion permeability and suggest that CFTR potentiates ATP release by stimulating a separate ATP channel to strengthen autocrine control of cell volume regulation.

Original languageEnglish (US)
Pages (from-to)6621-6630
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number9
DOIs
StatePublished - Mar 2 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Braunstein, G. M., Roman, R. M., Clancy, J. P., Kudlow, B. A., Taylor, A. L., Shylonsky, V. G., Jovov, B., Peter, K., Jilling, T., Ismailov, I. I., Benos, D. J., Schwiebert, L. M., Fitz, J. G., & Schwiebert, E. M. (2001). Cystic Fibrosis Transmembrane Conductance Regulator Facilitates ATP Release by Stimulating a Separate ATP Release Channel for Autocrine Control of Cell Volume Regulation. Journal of Biological Chemistry, 276(9), 6621-6630. https://doi.org/10.1074/jbc.M005893200