TRYPSIN INHIBITS PANCREATIC DUCTAL BICARBONATE SECRETION VIA PROTEASE-ACTIVATED RECEPTOR 2

Abstract

Background: Low doses of ethanol and bile acids stimulate pancreatic ductal bicarbonate secretion, whereas in high concentrations they will cause global inhibition of ion transport. Aim: To investigate the effects of trypsin on pancreatic duct cells. Methods: Intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were measured on isolated intra/interlobular microperfused guinea pig pancreatic ducts by microfluorimetry. Pancreatic protease-activated receptor 2 (PAR2) expression was determined by immunohistochemistry. Results: Luminal administration of trypsin or PAR2-AP had no effect on pHi in HCO3−-free solution, however in the presence of HCO3−, a marked pHi elevation was observed suggesting an inhibitory effect of a HCO3− efflux mechanism. Trypsin and PAR2-AP, even at low concentrations, activated Ca2+ signaling from the basal and luminal membranes of the duct cells. The soybean trypsin inhibitor or the Ca2+ chelator BAPTA-AM totally blocked the effect of trypsin on [Ca2+]i, whereas Ca2+-free external solution did not prevent this effect. PAR2 expression was found on the luminal membrane of intralobular, but not interlobular ducts. Conclusion: Our results suggest that the inhibition of pancreatic HCO3− secretion during the onset of acute pancreatitis may be mediated by the activation of PAR2.