Purinergic Receptors and Hepatobiliary Function

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This chapter describes the basic mechanisms that contribute to purinergic signaling in liver cells by focusing on a molecular and pharmacologic description of the receptors present, the mechanisms and regulation of adenosine triphosphate (ATP) release, and nucleotide/nucleoside degradation and reuptake pathways. In the liver, the progress in the identification of many contributors to purinergic signaling, including ATP channels, purinergic receptors, P-glycoproteins, and nucleotidases, suggests that extracellular nucleotides are likely to contribute to local the regulation of liver cells and organ function. In the liver, purinergic receptors are identified on the plasma membrane of the two principal epithelial cell types that form the bile secretory unit, including hepatocytes , which constitute liver parenchymal cells, and cholangiocytes , which line the lumen of intrahepatic bile ducts. The activation of purinergic receptors by selective binding of nucleotide or nucleoside agonists are linked to several fundamental responses important to cellular metabolism, ion channel activation, cell volume regulation, and bile formation. The chapter also reviews the potential roles of purinergic signaling in the regulation of liver-specific functions, including (1) hepatic metabolism/glycogenolysis, (2) cell volume regulation, and (3) secretion and bile formation.