BOMBESIN STIMULATES BICARBONATE SECRETION FROM RAT CHOLANGIOCYTES - IMPLICATIONS FOR NEURAL REGULATION OF BILE SECRETION

Background & Aims: Bombesin is a neuropeptide with many biological fun ctions 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 exa mined using isolated perfused rat livers, hepatocyte couplets, and iso lated bile duct units (IBDU) from rat liver. Results: Bombesin (100 nm ol/L) increased bile pH, bicarbonate concentration, and output in isol ated 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 i solated hepatocyte couplets. However, bombesin produced a dose-depende nt increase in secretion in IBDU, which was inhibited almost completel y by a specific bombesin receptor inhibitor, [Tyr(4), D-Phe(12)]-bombe sin (1 mu mol/L). This bombesin (10 nmol/L)-stimulated secretion in IB DU was accompanied by an increase in luminal pH and was dependent on b icarbonate 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 import ant regulatory role in biliary transport and secretion.