THE EFFECT OF BILE ACIDS ON PANCREATIC DUCTAL EPITHELIA

Abstract

Introduction: Exposure of the pancreas to bile acids is considered to be one of the possible causes of acute pancreatitis. However, no information is available on the effects of bile acids on intact pancreatic ductal epithelia. The aim of this study was to investigate the effect of various bile acids on pancreatic duct cells. Methods: Isolated guinea pig intra/interlobular pancreatic ducts were microperfused from the luminal and basolateral membranes. The effects of various bile acids /chenodeoxycholate, ursodeoxycholate and lithocholate/ on intracellular calcium concentration [Ca2+]i, and intracellular pH (pHi) were measured. Results: The exposure of intact ducts to all three primary bile acids induced a marked increase in [Ca2+]i and chenodeoxycholate caused the largest response. The effect of chenodeoxycholate from the luminal side was more pronounced than from the basolateral membrane. Furthermore, glycin conjugated bile acids, which are not membrane permeable, resulted in Ca2+ signals when administered from either side of the ducts. Calcium signals could still be triggered by bile acids in a Ca2+-free external solution, but preincubation of the ducts with an intracellular Ca2+-chelator, BAPTA-AM, totally abolished the effect of bile acids. Basolateral administration of chenodeoxycholate or glycochenodeoxycholate caused a reversible intracellular acidification. Conclusion: These results suggest the presence of bile acid transporters on guinea pig pancreatic duct cells. The transport of bile acids into duct cells leads to an increase in [Ca2+]i which is probably mediated via the release of calcium from intracellular stores. The bile acid-induced acidification of pancreatic ductal epithelia may play a role during acute pancreatitis. Supported by OTKA, MTA, OM.