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Endogenous prostaglandins modulate chloride secretion by prairie dog gallbladder

Journal of Laboratory and Clinical Medicine
Publication Date
DOI: 10.1016/s0022-2143(00)70024-2
  • Biology


Abstract In addition to concentrating bile, the gallbladder secretes chloride (Cl -) and mucus into its lumen. We recently observed that gallbladder Cl - secretion is increased in prairie dogs during the formation of cholesterol crystals, a period of altered mucosal prostaglandin synthesis. Pathologic Cl - secretion is characteristic of other epithelial disorders such as cystic fibrosis and hypercalciuric nephrolithiasis and may be important in gallstone pathogenesis. We hypothesized that concentrations of endogenous prostaglandin E 2 (PGE 2) found during experimental gallstone formation may mediate increased Cl - secretion by prairie dog gallbladder. Prairie dog gallbladders were harvested by cholecystectomy and mounted in Ussing chambers. Unidirectional transepithelial Cl -, Na +, and H 2O fluxes were measured before and after inhibition of endogenous prostaglandin synthesis with 10 μmol/L indomethacin. Gallbladders were then exposed to increasing concentrations of PGE 2 to a maximal dose of 1 μmol/L, as found in animals with gallstones. Standard electrophysiologic parameters were recorded simultaneously. Indomethacin increased mucosal resistance and stimulated gallbladder Na + and Cl - absorption. These effects were rapidly reversed by PGE 2. PGE 2 promoted Cl - secretion and decreased mucosal Na + absorption at concentrations found in the gallbladder bile of animals with gallstones. Endogenous prostaglandin metabolism modulates gallbladder Cl - secretion and may promote changes in Cl - transport associated with cholelithiasis. (J Lab Clin Med 2000;135:82-88)

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