Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes

Abstract

Background and Aims: Vasoactive intestinal polypeptide (VIP) is a neuropeptide with diverse biological functions including stimulatory effects on bile secretion. The effects of VIP on bile secretion and its site of action were examined. Methods: Choleretic effects of VIP were examined using isolated perfused livers, hepatocyte couplets, isolated bile duct units, and cholangiocytes from rat liver. Results: VIP (100 nmol/L) produced a small increase in bile flow and bile salt output in taurocholate-supplemented isolated perfused livers but had no significant effect on bile flow in the absence of bile salt supplements or on fluid secretion in isolated hepatocyte couplets. In addition, VIP significantly increased bile pH, bicarbonate concentration, and output in the isolated perfused livers from both normal and 2 week bile duct-ligated rats, although bile flow increased only in the bile duct-ligated model. VIP also produced a dose-dependent increase in fluid secretion in isolated bile duct units, which was inhibited significantly by VIP antagonist, a specific VIP receptor inhibitor. This VIP-stimulated secretory response in isolated bile duct units was more potent than those produced by bombesin or secretin. Neither somatostatin nor substance P inhibited the VIP response in isolated bile duct units. In contrast to secretin, VIP had no significant effect on adenosine 3',5'-cyclic monophosphate (cAMP) levels in isolated cholangiocytes. Conclusions: VIP is a potent stimulant of fluid and bicarbonate secretion from cholangiocytes via cAMP-independent pathways, suggesting that this neuropeptide plays a major regulatory role in biliary transport and secretion.