Effects of bile acids on dog pancreatic duct epithelial cell secretion and monolayer resistance.
Pancreatic duct epithelial cells (PDEC) mediate the secretion of fluid and electrolytes and are exposed to refluxed bile. In nontransformed cultured dog PDEC, which express many ion transport pathways of PDEC, 1 mM taurodeoxycholic acid (TDCA) stimulated an (125)I(-) efflux inhibited by DIDS and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and a (86)Rb(+) efflux inhibited by charybdotoxin. Inhibition by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM suggests mediation via increased intracellular Ca(2+) concentration, whereas the absence of lactate dehydrogenase release excludes cellular toxicity. At 1 mM, TDCA stimulated a larger (125)I(-) efflux than glycodeoxycholate; two dihydroxy bile acids, taurochenodeoxycholate and TDCA, were similarly effective, whereas a trihydroxy bile acid, taurocholate, was ineffective. In Ussing chambers, 1 mM serosal or 2 mM luminal TDCA stimulated an I(sc) increase from confluent PDEC monolayers. TDCA also stimulated 1) a short-circuit current (I(sc)) increase from basolaterally permeabilized PDEC subject to a serosal-to-luminal Cl(-) gradient that was inhibited by BAPTA-AM, DIDS, and NPPB and 2) an I(sc) increase from apically permeabilized PDEC subject to a luminal-to-serosal K(+) gradient inhibited by BAPTA-AM and charybdotoxin. Along with the efflux studies, these findings suggest that TDCA interacts directly with PDEC to stimulate Ca(2+)-activated apical Cl(-) channels and basolateral K(+) channels. Monolayer transepithelial resistance was only minimally affected by 1 mM serosal and 2 mM luminal TDCA but decreased after exposure to higher TDCA concentrations (2 mM serosal and 4 mM luminal). A secretory role for bile acids should be considered in pancreatic diseases associated with bile reflux.
Okolo
Charles
C
Division of Gastroenterology, Department of Medicine, University of Washington and Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA.
Wong
Thomas
T
Moody
Mark W
MW
Nguyen
Toan D
TD
D000818:Animals; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D013657:Taurodeoxycholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D007454:Iodides; D012414:Rubidium Radioisotopes; D013657:Taurodeoxycholic Acid; D007770:L-Lactate Dehydrogenase