title: Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig.
abstract: OBJECTIVE
  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 (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 HCO(3)(-) secretion, which was blocked by luminal H(2)DIDS (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 HCO(3)(-) secretion. Both CDC and GCDC elevated [Ca(2+)](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 HCO(3)(-) secretion, but did not modulate the inhibitory effect of high doses of CDC.
  
  
  CONCLUSIONS
  It is concluded that the HCO(3)(-) secretion stimulated by low concentrations of bile acids acts to protect the pancreas against toxic bile, whereas inhibition of HCO(3)(-) secretion by high concentrations of bile acids may contribute to the progression of acute pancreatitis.
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: V
authors.initials: V
authors.lastname: Venglovecz
authors.forename: Z
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: B
authors.initials: B
authors.lastname: Ozsvári
authors.forename: T
authors.initials: T
authors.lastname: Takács
authors.forename: J
authors.initials: J
authors.lastname: Lonovics
authors.forename: A
authors.initials: A
authors.lastname: Varró
authors.forename: M A
authors.initials: MA
authors.lastname: Gray
authors.forename: B E
authors.initials: BE
authors.lastname: Argent
authors.forename: P
authors.initials: P
authors.lastname: Hegyi
mesh_terms: D000208:Acute Disease; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005999:Glycochenodeoxycholic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008969:Molecular Sequence Data; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D001639:Bicarbonates; D001647:Bile Acids and Salts; D027963:Chloride-Bicarbonate Antiporters; D002635:Chenodeoxycholic Acid; D005999:Glycochenodeoxycholic Acid; D002118:Calcium