Статья

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

Gavin M. BraunsteinDepartment of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USARichard M. Roman§Division of Hepatology, University of Colorado Health Sciences Center, Denver, Colorado, 80262, and theJohn Clancy‖Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, theBrian A. KudlowDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Amanda L. Taylor¶Gregory Fleming James Cystic Fibrosis Research Center,Vadim Gh. Shylonsky‡Department of Physiology and Biophysics,Biljana JovovDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Krisztina PeterDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Tamás JillingDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Iskander I. IsmailovDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Dale BenosDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Lisa M. SchwiebertDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201Johanna Fitz§Division of Hepatology, University of Colorado Health Sciences Center, Denver, Colorado, 80262, and theErik M. SchwiebertDepartment of Pediatrics, The Evanston Hospital, Evanston, Illinois 60201

2001en

ABI

Аннотация

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 (Gd(3+)) 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.

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Идентификаторы

DOI: 10.1074/jbc.m005893200

Цитирования и источники

Цитирований: 5Использованных источников: 0

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