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J. Biol. Chem., Vol. 276, Issue 9, 6621-6630, March 2, 2001
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From the 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.
Cystic Fibrosis Transmembrane Conductance Regulator
Facilitates ATP Release by Stimulating a Separate ATP Release Channel
for Autocrine Control of Cell Volume Regulation*
,
,¶,,,,,¶,¶**,¶**§§
Department of Physiology and Biophysics,
** Department of Cell Biology, ¶ Gregory Fleming James Cystic
Fibrosis Research Center, Department of Pediatrics, University
of Alabama at Birmingham, Birmingham, Alabama 35294-0005, the
§ Division of Hepatology, University of Colorado Health
Sciences Center, Denver, Colorado, 80262, and the
Department of Pediatrics, The Evanston
Hospital, Evanston, Illinois 60201
*
This work was supported by a CF New Investigator Grant from
the Cystic Fibrosis Foundation (CFF) (to E. M. S.), by
National Institutes of Health Grant R01 DK/HL 54367 (to E. M. S.), by a CF New Investigator Grant and Research Grant from the CFF (to L. M. S.), by an National Institutes of Health Grant DK-48764 (to D. J. B.), by a CFF Fellowship F981 (to B. J.), and
by a Leroy Matthews award from the CFF (to J. P. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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