ROLE OF THE NEUROPEPTIDE, BOMBESIN, IN BILE SECRETION

Since ancient times, bile secretion has been considered vital for main taining health. One of the main functions of bile secretion is gastric acid neutralization with biliary bicarbonate during a meal or Pavlovi an response. Although the liver has many extrinsic and intrinsic nerve innervations, the functional role of these nerves in biliary physiolo gy is poorly understood. To understand the role of neural regulation i n bile secretion, our recent studies on the effect of bombesin, a neur opeptide, on bile secretion and its underlying mechanisms will be revi ewed. Using isolated perfused rat livers (IPRL) from both normal and 2 week bile duct ligated rats, as well as hepatocyte couplets and isola ted bile duct units (IBDU) from normal rat livers, bombesin was shown to stimulate biliary bicarbonate and fluid secretion from bile ducts. Detailed pH studies indicated that bombesin stimulated the activity of Cl-/HCO3- exchanger, which was counterbalanced by a secondary activat ion of electrogenic Na+/HCO3- symport. Quantitative videomicroscopic s tudies showed that bombesin-stimulated fluid secretion in IBDU was dep endent on Cl- and HCO3- in the media, anion exchanger(s), Cl- and K+ c hannels, and carbonic anhydrase, but not on the microtubular system. F urthermore. this bombesin response is inhibited by somatostatin but no t substance P. Finally, studies of secondary messengers in isolated ch olangiocytes and IBDU indicated that bombesin had no effect on intrace llular cAMP, cGMP, or Ca++ levels in cholangiocytes. These results pro vide evidence that neuropeptides such as bombesin can directly stimula te fluid and bicarbonate secretion from cholangiocytes by activating l uminal Cl-/HCO3- exchange, but by different mechanisms from those esta blished for secretin. These findings, in turn, suggest that neuropepti des may play an important regulatory role in biliary transport and sec retion. Thus, this neuropeptidergic regulation of bile secretion may p rovide a plausible mechanism for the bicarbonate-rich choleresis seen with meals or Pavlovian response.