Octreotide stimulates Ca++ secretion by the gallbladder: A risk factor for gallstones

Abstract

Background: Gallstone formation during octreotide therapy has been linked to elevated levels of gallbladder bile Ca ++, a well-known prolithogenic factor. Although the subcutaneous administration of octreotide raises gallbladder bile Ca ++ in prairie dogs, the mechanism for this effect is unknown. Octreotide has been shown to increase gallbladder Na + and water absorption in Ussing chamber studies. Given the known effects of octreotide on gallbladder ion transport, we hypothesized that octreotide may also promote gallstone formation by stimulating gallbladder Ca ++ secretion, thereby raising the lumenal concentration of biliary Ca ++. Methods: After cholecystectomy, prairie dog gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded. Unidirectional fluxes of Ca ++ and Na + were measured before and after serosal exposure to 50 nmol/L octreotide. Results: Under basal conditions normal prairie dog gallbladder absorbed mucosal Ca ++. Serosal octreotide converted the gallbladder from a state of basal Ca ++ absorption to one of net Ca ++ secretion by stimulating serosa to mucosa Ca ++ flux. As anticipated, octreotide increased net Na + absorption by stimulating mucosa to serosa Na + flux and decreased tissue conductance and short-circuit current significantly compared with baseline values. Conclusion: Fifty nanomoles per liter octreotide stimulated Ca ++ secretion by gallbladder epithelium, a possible mechanism for increased biliary Ca ++ in prairie dogs receiving subcutaneous injections. Ca ++ secretion linked to octreotide therapy may induce gallstones by raising biliary levels of Ca ++, a known prolithogenic factor. (Surgery 1999;125:509-13.)