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

Background. Gallstone formation during octreotide therapy has been linked t o elevated levels of gallbladder bile Ca++, a well-known prolithogenic fact or. Although the subcutaneous administration of octreotide raises gallbladd er bile Ca++ in prairie dogs, the mechanism for this effect is unknown. Oct reotide has been shown to increase gallbladder Na+ and water absorption in Ussing chamber studies. Given the known effects of octreotide on gallbladde r ion transport, we hypothesized that octreotide may also promote gallstone formation by stimulating gallbladder Ca++ secretion, thereby raising the l umenal concentration of biliary Ca++. Methods. After cholecystectomy, prairie dog gallbladders were mounted in Us sing chambers, and standard electrophysiologic parameters were recorded. Un idirectional 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 muc osal Ca++. Serosal octreotide converted the gallbladder from a state of bas al Ca++ absorption to one of net Ca++ secretion by stimulating serosa to mu cosa 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.