Domain-specific purinergic signaling in polarized rat cholangiocytes

Kelli D. Salter, J. Gregory Fitz, Richard M. Roman

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


In cholangiocytes, adenine nucleotides function as autocrine/paracrine signals that modulate ductular ion transport by activation of purinergic receptors. The purpose of these studies was to identify cellular signals that modulate ATP release and nucleotide processing in polarized normal rat cholangiocytes. In Ussing chamber studies, selective exposure of the apical and basolateral membranes to ATP or adenosine 5'-O-(3-thiotriphosphate) (ATPγS) stimulated increases in short-circuit current. Apical purinergic receptor agonist preference was consistent with the P2Y2 subtype. In contrast, basolateral ADP was more potent in stimulating transepithelial currents, consistent with the expression of different basolateral P2 receptor(s). Luminometric analysis revealed that both membranes exhibited constitutive ATP efflux. Hypotonic exposure enhanced ATP release in both compartments, whereas decreases in ATP efflux during hypertonicity were more prominent at the apical membrane. Increases in intracellular cAMP, cGMP, and Ca2+ also increased ATP permeability, but selective effects on apical and basolateral ATP release differed. Finally, the kinetics of ATP degradation in apical and basolateral compartments were distinct. These findings suggest that there are domain-specific signaling pathways that contribute to purinergic responses in polarized cholangiocytes.

Original languageEnglish (US)
Pages (from-to)G492-G500
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3 41-3
StatePublished - Mar 2000


  • Adenosine 5'-triphosphate release and processing
  • Extracellular nucleotides
  • P2 receptors
  • Transepithelial ion transport

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


Dive into the research topics of 'Domain-specific purinergic signaling in polarized rat cholangiocytes'. Together they form a unique fingerprint.

Cite this