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Bicarbonate‐rich choleresis induced by secretin in normal rat is taurocholate‐dependent and involves AE2 anion exchanger
Author(s) -
Banales Jesús M.,
Arenas Fabián,
RodríguezOrtigosa Carlos M.,
Sáez Elena,
Uriarte Iker,
Doctor R. Brian,
Prieto Jesús,
Medina Juan F.
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21042
Subject(s) - secretin , medicine , dids , chemistry , bicarbonate , endocrinology , choleretic , bile salt export pump , bile acid , excretion , secretion , biochemistry , transporter , membrane , gene
Canalicular bile is modified along bile ducts through reabsorptive and secretory processes regulated by nerves, bile salts, and hormones such as secretin. Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR)–dependent Cl − efflux and subsequent biliary HCO 3 − secretion, possibly via Cl − /HCO 3 − anion exchange (AE). However, the contribution of secretin to bile regulation in the normal rat, the significance of choleretic bile salts in secretin effects, and the role of Cl − /HCO 3 − exchange in secretin‐stimulated HCO 3 − secretion all remain unclear. Here, secretin was administered to normal rats with maintained bile acid pool via continuous taurocholate infusion. Bile flow and biliary HCO 3 − and Cl − excretion were monitored following intrabiliary retrograde fluxes of saline solutions with and without the Cl − channel inhibitor 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoic acid (NPPB) or the Cl − /HCO 3 − exchange inhibitor 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS). Secretin increased bile flow and biliary excretion of HCO 3 − and Cl − . Interestingly, secretin effects were not observed in the absence of taurocholate. Whereas secretin effects were all blocked by intrabiliary NPPB, DIDS only inhibited secretin‐induced increases in bile flow and HCO 3 − excretion but not the increased Cl − excretion, revealing a role of biliary Cl − /HCO 3 − exchange in secretin‐induced, bicarbonate‐rich choleresis in normal rats. Finally, small hairpin RNA adenoviral constructs were used to demonstrate the involvement of the Na + ‐independent anion exchanger 2 (AE2) through gene silencing in normal rat cholangiocytes. AE2 gene silencing caused a marked inhibition of unstimulated and secretin‐stimulated Cl − /HCO 3 − exchange. In conclusion , maintenance of the bile acid pool is crucial for secretin to induce bicarbonate‐rich choleresis in the normal rat and that this occurs via a chloride–bicarbonate exchange process consistent with AE2 function. (H EPATOLOGY 2006;43:266–275.)