Bombesin stimulates bicarbonate secretion from rat cholangiocytes: Implications for neural regulation of bile secretion

Background & Aims: Bombesin is a neuropeptide with many biological functions and is known to stimulate bile secretion. The aim of this study was to determine the role of bombesin in bile secretion and its site of action. Methods: The effects of bombesin on bile secretion were examined using isolated perfused rat livers, hepatocyte couplets, and isolated bile duct units (IBDU) from rat liver. Results: Bombesin (100 nmol/L) increased bile pH, bicarbonate concentration, and output in isolated perfused rat livers from both normal and 2-week bile duct-ligated vats, although bile flow increased only in the latter model. Bombesin (10-100 nmol/L) also had no effect on canalicular bile secretion in isolated hepatocyte couplets. However, bombesin produced a dose-dependent increase in secretion in IBDU, which was inhibited almost completely by a specific bombesin receptor inhibitor, [Tyr(4), D-Phe(12)]-bombesin (1 mu mol/L). This bombesin (10 nmol/L)-stimulated secretion in IBDU was accompanied by an increase in luminal pH and was dependent on bicarbonate and chloride in the medium. Somatostatin but not substance P inhibited the bombesin response. Conclusions: Neuropeptides such as bombesin can directly stimulate fluid and bicarbonate secretion at the level of cholangiocytes, suggesting that neuropeptides play an important regulatory role in biliary transport and secretion.