INTRACELLULAR PH REGULATION IN BOMBESIN-STIMULATED SECRETION IN ISOLATED BILE-DUCT UNITS FROM RAT-LIVER

Bombesin, a neuropeptide, stimulates fluid and HCO3- secretion from ch olangiocytes, but the underlying mechanisms are poorly understood. In this study, we aimed to examine the effects of bombesin on ion transpo rt processes involved in the regulation of intracellular pH (pH(i)) an d HCO3- secretion in polarized cholangiocytes. Isolated bile duct unit s from normal rat liver were used to measure pH(i) by 2',7'-bis(2-carb oxyethyl)-5(6)-carboxyfluorescein 495 nm-to-440 nm dual ratio methods. Bombesin increased Cl--HCO3- exchange activity but did not affect bas al pH(i) or the activities of Na+/H+ exchange or Na+-HCO3- symport. De polarization of cholangiocytes increased basal pH(i) and the activity of Cl-/HCO3- exchange, suggesting that an electrogenic Na+-HCO3- sympo rt might function as a counterregulatory pH(i) mechanism. Na+-independ ent acid-extruding mechanisms were not observed. We conclude that bomb esin stimulates biliary secretion from cholangiocytes by activating lu minal Cl-/HCO3- exchange, which may be coupled to basolateral electrog enic Na+-HCO3- symport.