Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig

Viktória Venglovecz ¹, Zoltan Rakonczay Jr.¹, Bela Ozsvari ¹, Tamas Takacs ¹, Janos Lonovics ¹, Andras Varro ¹, Mike A Gray ², Barry E Argent ² and Peter Hegyi ^1*

¹ First Department of Medicine, University of Szeged, Hungary
² Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, United Kingdom

^* To whom correspondence should be addressed. E-mail: hep{at}in1st.szote.u-szeged.hu.

Accepted 15 February 2008

Abstract

Background. Acute pancreatitis is associated with significant morbidity and mortality. Bile reflux into the pancreas is a common cause of acute pancreatitis and although the bile can reach both acinar and ductal cells most research to date has focused on the acinar cells. Our aim was to investigate the effects of bile acids on HCO₃^- secretion from the ductal epithelium.

Methods. Isolated guinea pig intra/interlobular pancreatic ducts were microperfused and the effects of unconjugated chenodeoxycholate (CDC) and conjugated glycochenodeoxycholate (GCDC) on intracellular calcium concentration ([Ca²⁺]_i) and pH (pH_i) were measured using fluorescent dyes. Changes of pH_i were used to calculate the rates of acid/base transport across the duct cell membranes.

Results. Luminal administration of a low dose of CDC (0.1 mM) stimulated ductal HCO₃^- secretion, which was blocked by luminal H₂DIDS. In contrast, both luminal and basolateral administration of a high dose of CDC (1 mM) strongly inhibited HCO₃^- secretion. Both CDC and GCDC elevated [Ca²⁺]_i and this effect was blocked by BAPTA-AM, caffeine, xestospongin C and the PLC inhibitor U73122. BAPTA-AM also inhibited the stimulatory effect of low doses of CDC on HCO₃^- secretion, but did not modulate the inhibitory effect of high doses of CDC.

Conclusions. We conclude that the HCO₃^- secretion stimulated by low concentrations of bile acids acts to protect the pancreas against toxic bile, whereas inhibition of HCO₃^- secretion by high concentrations of bile acids may contribute to the progression of acute pancreatitis.