DIFERENTIAL EFFECTS OF BILE ACIDS ON PANCREATIC DUCTAL BICARBONATE SECRETION

Abstract

Background & Aims: Acute pancreatitis is a serious disease which is associated with significant morbidity and mortality. Bile reflux into the pancreas is one of the commonest causes of acute pancreatitis. Although the bile can reach both acinar and ductal cells during biliary pancreatitis, much more research has been done on acinar cells. Our aim was to characterize the effects of bile acids on HCO3- secretion from ductal epithelia. Methods: Isolated guinea pig intra/interlobular pancreatic ducts were microperfused from the luminal and/or basolateral membranes. The effects of chenodeoxycholate (CDC) and glycochenodeoxycholate (GCDC) on intracellular calcium concentration and pH were measured using fluorescent dyes by microfluorometry. Changes of intracellular pH were measured to estimate the HCO3- and H+ transport across the membrane. Results: Luminal administration of a low dose (0.1mM) of CDC stimulated HCO3- secretion which could be blocked by luminal administration of H2DIDS. In contrast, either luminal or basolateral administration of high dose (1mM) of CDC strongly inhibited ductal HCO3- secretion. Both CDC and GCDC elevated intracellular calcium concentration and this effect was blocked by BAPTA-AM and caffeine. BAPTA-AM inhibited the stimulatory effect of low doses of CDC on HCO3- secretion, but did not modulate the inhibitory effect of high does of CDC. Conclusions: We conclude that the stimulated HCO3- and fluid secretion by low concentrations of bile acids protect the pancreas against the toxic bile, whereas inhibition of secretion by high concentrations of bile acid s may contribute to the progression of acute pancreatitis.