Octreotide promotes gallbladder absorption in prairie dogs: a potential cause of gallstones.
OBJECTIVE
Gallstone formation during octreotide administration has been causally linked to increased biliary concentrations of calcium, protein, and total lipids, all purported prolithogenic factors. These changes may be caused by octreotide-induced gallbladder stasis or a direct effect of octreotide on gallbladder absorption. We tested the hypothesis that octreotide stimulates gallbladder ion and water transport.


METHODS
Prairie dog gallbladders were mounted in Ussing chambers and bathed in oxygenated Ringer's solution. Electrophysiological parameters were recorded, and unidirectional Na+, Cl-, and H2O fluxes were measured before and after serosal exposure to 50 nmol/L octreotide.


RESULTS
Octreotide exposure caused a significant decrease in transepithelial short-circuit current and potential difference and an increase in tissue resistance compared with baseline. These alterations in electrophysiological parameters coincided with changes in ion transport. Octreotide stimulated net Na+ and H2O absorption and converted the gallbladder from a state of Cl- secretion to one of Cl- absorption by increasing mucosal to serosal fluxes. Octreotide effects on ion transport were blocked by 4,4'-diisothiocynostilbene-2,2'-disulfonic acid and amiloride and reversed by theophylline.


CONCLUSIONS
Octreotide may promote gallstone formation by inducing gallbladder stasis and by directly increasing gallbladder absorption, which may act synergistically to increase the concentration of prolithogenic factors in bile and to facilitate nucleation and stone growth.
Moser
A J
AJ
Department of Surgery, UCLA School of Medicine, USA.
Abedin
M Z
MZ
Giurgiu
D I
DI
Roslyn
J J
JJ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000042:Absorption; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D002769:Cholelithiasis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004594:Electrophysiology; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D015282:Octreotide / Q000009:adverse effects*; D012589:Sciuridae; D012704:Serous Membrane / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D014867:Water / Q000378:metabolism
D002712:Chlorides; D014867:Water; D012964:Sodium; D013806:Theophylline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D015282:Octreotide