Evidence for Gd3+ inhibition of membrane ATP permeability and purinergic signaling

Richard M. Roman, Andrew P. Feranchak, Amy K. Davison, Erik M. Schwiebert, J. Gregory Fitz

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Abstract

Extracellular ATP functions as an important autocrine and paracrine signal that modulates a broad range of cell and organ functions through activation of purinergic receptors in the plasma membrane. Because little is known of the cellular mechanisms involved in ATP release, the purpose of these studies was to evaluate the potential role of the lanthanide Gd3+ as an inhibitor of ATP permeability and to assess the physiological implications of impaired purinergic signaling in liver cells. In rat hepatocytes and HTC hepatoma cells, increases in cell volume stimulate ATP release, and the localized increase in extracellular ATP increases membrane Cl- permeability and stimulates cell volume recovery through activation of P2 receptors. In cells in culture, spontaneous ATP release, as measured by a luciferin- luciferase-based assay, was always detectable under control conditions, and extracellular ATP concentrations increased 2- to 14-fold after increases in cell volume. Gd3+ (200 μM) inhibited volume-sensitive ATP release by >90% (P < 0.001), inhibited cell volume recovery from swelling (P < 0.01), and uncoupled cell volume from increases in membrane Cl- permeability (P < 0.01). Moreover, Gd3+ had similar inhibitory effects on ATP release from other liver and epithelial cell models. Together, these findings support an important physiological role for constitutive release of ATP as a signal coordinating cell volume and membrane ion permeability and suggest that Gd3+ might prove to be an effective inhibitor of ATP-permeable channels once they are identified.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume277
Issue number6 40-6
Publication statusPublished - Dec 1999

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Keywords

  • Cell volume
  • Chloride channel
  • Liver

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

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