Document Detail

Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation.
MedLine Citation:
PMID:  8876255     Owner:  NLM     Status:  MEDLINE    
Recovery of cell volume in response to osmotic stress is mediated in part by increases in the Cl- permeability of the plasma membrane. These studies evaluate the hypothesis that ATP release and autocrine stimulation of purinergic (P2) receptors couple increases in cell volume to opening of Cl- channels. In HTC rat hepatoma cells, swelling induced by hypotonic exposure increased membrane Cl- current density to 44.8 +/- 7.1 pA/pF at -80 mV. Both the rate of volume recovery and the increase in Cl- permeability were inhibited in the presence of the ATP hydrolase apyrase (3 units/ml) or by exposure to the P2 receptor blockers suramin and Reactive Blue 2 (10-100 microM). Cell swelling also stimulated release of ATP. Hypotonic exposure increased the concentration of ATP in the effluent of perfused cells by 170 +/- 36 nM in the presence of a nucleotidase inhibitor (P < 0.01). In whole-cell recordings with ATP as the charge carrier, cell swelling increased membrane current density approximately 30-fold to 16.5 +/- 10.4 pA/pF. These findings indicate that increases in cell volume lead to efflux of ATP through opening of a conductive pathway consistent with a channel, and that extracellular ATP is required for recovery from swelling. ATP may function as an autocrine factor that couples increases in cell volume to opening of Cl- channels through stimulation of P2 receptors.
Y Wang; R Roman; S D Lidofsky; J G Fitz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  93     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-12-04     Completed Date:  1996-12-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  12020-5     Citation Subset:  IM    
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Adenosine Triphosphate / analogs & derivatives,  metabolism*,  pharmacology
Apyrase / pharmacology
Cell Membrane / physiology
Chloride Channels / physiology*
Chlorides / metabolism
Hypotonic Solutions
Liver Neoplasms, Experimental / pathology*,  physiopathology
Models, Biological
Receptors, Purinergic P2 / drug effects,  physiology*
Signal Transduction
Suramin / pharmacology
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Chloride Channels; 0/Chlorides; 0/Hypotonic Solutions; 0/Receptors, Purinergic P2; 145-63-1/Suramin; 35094-46-3/adenosine 5'-O-(3-thiotriphosphate); 56-65-5/Adenosine Triphosphate; EC

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