The role of neurotensin in human gallbladder motility

Gallbladder contraction in response to a fatty meal is thought to be caused by release of cholecystokinin (CCK). We have previously demonstrated a close correlation between circulating concentrations of CCK and contraction of the gallbladder in normal humans and in gallstone patients. Recent studies in animals, however, have shown that other potentially cholecystokinetic hormonal agents are released by a fatty meal, which suggests that other hormones may be involved in postprandial gallbladder contraction. Neurotensin, a 13-amino acid peptide, is released by fat; we have shown it to cause gallbladder contraction in dogs. In the present study, we measured release of neurotensin in seven normal adult volunteers. We determined the effects of infused neurotensin (4 pmol/kg-min) on gallbladder contractility, measured by ultrasonography in 10 adult volunteers, and we evaluated release of neurotensin in eight patients with gallstones. After ingestion of fat, we found significant release of neurotensin in normal volunteers from a mean basal concentration of 15.9 +/- 3.5 pg/ml to a maximum of 34.7 +/- 0.2 pg/ml. In the gallstone patients after fat ingestion, neurotensin rose from a basal of 16.8 +/- 3.1 pg/ml to a maximum of 53.4 +/- 28.1 pg/ml, which was a significantly greater release than in controls. Intravenous infusion of neurotensin produced dilatation of the gallbladder (from a mean basal volume of 13.7 +/- 2.3 cc to 20.0 +/- 1.8 cc). Neurotensin causes relaxation of the gallbladder in humans and, by contributing to stasis, may be involved in the formation of gallstones.