Intracellular pH regulation in bombesin-stimulated secretion in isolated bile duct units from rat liver

Bombesin, a neuropeptide, stimulates fluid and HCO3- secretion from cholangiocytes, but the underlying mechanisms are poorly understood. In this study, we aimed to examine the effects of bombesin on ion transport processes involved in the regulation of intracellular pH (pH(i)) and HCO3- secretion in polarized cholangiocytes. Isolated bile duct units from normal rat liver were used to measure pH(i) by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein 495 nm-to-440 nm dual ratio methods. Bombesin increased Cl--HCO3- exchange activity but did not affect basal pH(i) or the activities of Na+/H+ exchange or Na+-HCO3- symport. Depolarization of cholangiocytes increased basal pH(i) and the activity of Cl-/HCO3- exchange, suggesting that an electrogenic Na+-HCO3- symport might function as a counterregulatory pH(i) mechanism. Na+-independent acid-extruding mechanisms were not observed. We conclude that bombesin stimulates biliary secretion from cholangiocytes by activating luminal Cl-/HCO3- exchange, which may be coupled to basolateral electrogenic Na+-HCO3- symport.