Endogenous prostaglandins modulate chloride secretion by prairie dog gallbladder

In addition to concentrating bile, the gallbladder secretes chloride (Cl-) and mucus into ifs lumen. We recently observed that gallbladder Cl- secreti on is increased in prairie dogs during the formation of cholesterol crystal s, a period of altered mucosal prostaglandin synthesis. Pathologic Cl- secr etion is characteristic of other epithelial disorders such as cystic fibros is and hypercalciuric nephrolithiasis and may be important in gallstone pat hogenesis. We hypothesized that concentrations of endogenous prostaglandin E-2 (PGE(2)) found during experimental gallstone formation may mediate incr eased Cl- secretion by prairie dog gallbladder, Prairie dog gallbladders we re harvested by cholecystectomy and mounted in Ussing chambers. Unidirectio nal transepithelial Cl-, Na+, and H2O fluxes were measured before and after inhibition of endogenous prostaglandin synthesis with 10 mu mol/L indometh acin. Gallbladders were then exposed to increasing concentrations of PGE(2) to a maximal dose of 1 mu mol/L, as found in animals with gallstones. Stan dard electrophysiologic parameters were recorded simultaneously. Indomethac in increased mucosal resistance and stimulated gallbladder Na+ and CI- abso rption. These effects were rapidly reversed by PGE(2). PGE(2) promoted Cl- secretion and decreased mucosal Na+ absorption at concentrations found in t he gallbladder bile of animals with gallstones. Endogenous prostaglandin me tabolism modulates gallbladder CI- secretion and may promote changes in Cl- transport associated with cholelithiasis.