title: Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation.
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 (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.
authors: Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
authors: G M
authors: GM
authors: Braunstein
authors: R M
authors: RM
authors: Roman
authors: J P
authors: JP
authors: Clancy
authors: B A
authors: BA
authors: Kudlow
authors: A L
authors: AL
authors: Taylor
authors: V G
authors: VG
authors: Shylonsky
authors: B
authors: B
authors: Jovov
authors: K
authors: K
authors: Peter
authors: T
authors: T
authors: Jilling
authors: I I
authors: II
authors: Ismailov
authors: D J
authors: DJ
authors: Benos
authors: L M
authors: LM
authors: Schwiebert
authors: J G
authors: JG
authors: Fitz
authors: E M
authors: EM
authors: Schwiebert
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D048429:Cell Size; D018118:Chloride Channels / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D005682:Gadolinium; C038958:gadolinium chloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid