Article Text

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


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 HCO3 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 ([Ca2+]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 HCO3 secretion, which was blocked by luminal H2DIDS (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.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Digest
    Robin Spiller Magnus Simren
  • Commentary
    Min Goo Lee Shmuel Muallem