Endogenous ATP release regulates Cl- secretion in cultured human and rat biliary epithelial cells

Richard M. Roman, Andrew P. Feranchak, Kelli D. Salter, Yu Wang, J. Gregory Fitz

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

P2Y receptor stimulation increases membrane Cl- permeability in biliary epithelial cells, but the source of extracellular nucleotides and physiological relevance of purinergic signaling to biliary secretion are unknown. Our objectives were to determine whether biliary cells release ATP under physiological conditions and whether extracellular ATP contributes to cell volume regulation and transepithelial secretion. With the use of a sensitive bioluminescence assay, constitutive ATP release was detected from human Mz-ChA-1 cholangiocarcinoma cells and polarized normal rat cholangiocyte monolayers. ATP release increased rapidly during cell swelling induced by hypotonic exposure. In Mz-ChA-1 cells, removal of extracellular ATP (apyrase) and P2 receptor blockade (suramin) reversibly inhibited whole cell Cl- current activation and prevented cell volume recovery during hypotonic stress. Moreover, exposure to apyrase induced cell swelling under isotonic conditions. In intact normal rat cholangiocyte monolayers, hypotonic perfusion activated apical Cl- currents, which were inhibited by addition of apyrase and suramin to bathing media. These findings indicate that modulation of ATP release by the cellular hydration state represents a potential signal coordinating cell volume with membrane Cl- permeability and transepithelial Cl- secretion.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number6 39-6
StatePublished - Jun 1999

Fingerprint

Adenosine Triphosphate
Epithelial Cells
Apyrase
Cell Size
Suramin
Permeability
Membranes
Cholangiocarcinoma
Osmotic Pressure
Nucleotides
Perfusion

Keywords

  • Cell volume
  • Chloride channel
  • Cholangiocyte
  • Nucleotide

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Endogenous ATP release regulates Cl- secretion in cultured human and rat biliary epithelial cells. / Roman, Richard M.; Feranchak, Andrew P.; Salter, Kelli D.; Wang, Yu; Fitz, J. Gregory.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 276, No. 6 39-6, 06.1999.

Research output: Contribution to journalArticle

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