Regulation of biliary secretion by extracellular nucleotides

Bile formation is an essential function of the liver and depends upon complimentary actions of hepatocytes and intrahepatic bile duct cells, or cholangiocytes. Cholangiocytes contribute importantly to the volume and composition of bile secreted by the liver through absorption and secretion of fluid and electrolytes. Biophysical measurements suggest that increases in Cl^- permeability at the apical membrane of cholangiocytes represent an important cellular site for regulation of secretion. Recent evidence suggests that extracellular ATP may serve as a signal modifying cholangiocyte secretion through the regulation of membrane Cl^- permeability. Through activation of P_2Y2 receptors in the apical (luminal) membrane of cholangiocytes, ATP functions as a local autocrine/paracrine regulatory factor that modulates biliary secretion. Consequently, the purpose of this review is to describe the cellular mechanisms thought to contribute to ATP release and review the evidence supporting a role for ATP in the regulation of cholangiocyte Cl^- secretion and bile formation. Characterization of the factors that regulate local nucleotide concentrations and purinergic signaling may represent therapeutic targets for the pharmacologic modulation of bile composition and flow.