Dual effects of bile acids on guinea pig pancreatic ductal bicarbonate secretion

Abstract

Aims: 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 epithelia. Methods: Isolated guinea pig intra/interlobular pancreatic ducts were perfused from the luminal and basolateral membranes with standard Hepes or HCO3-/CO2 solutions. The effects of chenodeoxycholate (non-conjugated bile acid, CDC) and glycochenodeoxycholate (conjugated bile acid, GCDC) on intracellular pH (pHi) of pancreatic ductal epithelial cells (PDEC) were measured using the fluorescent dye BCECF and microfluorometry. Results: Basolateral or luminal administration of the membrane permeable CDC dose dependently decreased the pHi of PDEC. However, GCDC decreased the pHi mostly from the basolateral side, suggesting that functionally active bile acid transporters are expressed in PDEC. Moreover, luminal administration of low doses (100µM) of CDC significantly stimulated the HCO3- secretion of PDEC, most likely via the luminal anion exchanger. Neither basolateral exposure of low doses of CDC nor low or high doses (100µM and 1000µM, respectively) of GCDC (administered either from the basolateral or luminal side) had an effect on ductal HCO3- secretion. Interestingly, basolateral or luminal administration of high doses (1000µM) of CDC inhibited HCO3- secretion. Low doses of bile acids had no effect on the activities of the Na+/HCO3- cotransporter and the Na+/H+ exchanger. On the other hand, high doses (1000µM) of CDC inhibited the above mentioned acid/base transporters localised on the basolateral membrane of PDEC. Conclusion: These results suggest the presence of specific bile acid transporters in PDEC. Low doses of CDC stimulate pancreatic HCO3- secretion which may serve as a defence mechanism during acute pancreatitis. The inhibition of acid/base transporters by high doses of CDC is probably due to the marked acidification (toxic effect) caused by this non-conjugated bile acid. This work was supported by OTKA, MTA, OM and Royal Society.