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

V. Venglovecz, Z. Rakonczay, B. Ózsvári, T. Takács, J. Lonovics, A. Varro, M. A. Gray, B. E. Argent, Péter Hegyi

Research output: Article

66 Citations (Scopus)

Abstract

Background and aims: 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. The aim of the present study was to investigate the effects of bile acids on HCO 3- secretion from the ductal epithelium. Methods: Isolated guinea pig intralobular/interlobular pancreatic ducts were microperfused and the effects of unconjugated chenodeoxycholate (CDC) and conjugated glycochenodeoxycholate (GCDC) on intracellular calcium concentration ([Ca 2+]i) and pH (pHi) were measured using fluorescent dyes. Changes of pHi 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 HCO 3- secretion, which was blocked by luminal H 2DIDS (dihydro-4,4′-diisothiocyanostilbene-2,2′- disulfonic acid). 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 (1,2-bis(o-aminophenoxy)ethane-N,N,N′, N′-tetra-acetic acid), caffeine, xestospongin C and the phospholipase C 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: It is concluded 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.

Original languageEnglish
Pages (from-to)1102-1112
Number of pages11
JournalGut
Volume57
Issue number8
DOIs
Publication statusPublished - aug. 1 2008

ASJC Scopus subject areas

  • Gastroenterology

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