Secretin stimulated bile salt independent bile flow and ae2 mediated anion exchange

Resumen

canalicular bile is modified along bile duets through reabsorptive and secretory processes reguiated by nerves, bile salts, and hormones like secretin. secretin stimulates ductular CFTR-dependent cl- efflux and subsequent biliary HC03-secretion, possibly via C1-/HC03- anión exchange (AE). But the contribution of secretin to bile reguiation in the normal rat, the signi fi canee of choleretic bile salts in secretin effeets and the role of C1-/HC03- exchange in secretin-stimulated HC03- secretion all remain unclear. Here, secretin was administered to normal rats with maintained bile acid pool via continuous taurocholate infusión. Bile flow and biliary HC03- and Cl- excretion were monitored following intrabiliary retrograde fluxes of saline solutions with and without the Cl- channel inhibitor NPPB or the C1-/HC03- exchange inhibitor DIDS. Secretin increased bile flow and biliary excretion of hc03- and Cl-, interestingly, secretin effects were not observed in the absence of taurocholate. While secretin effects were all blocked by intrabiliary NPPB, DIDS only inhibited secretin-induced increases in bile flow and HC03- excretion but not the increased Cl- excretion, thus evidencing a role of biliary C1-/HC03-exchange in secretin-induced bicarbonate-rich cnoleresis in normal rats. Finally, small-hairpin-RNA adenoviral constructs were used to demónstrate the involvement of the ae2 C1-/HC03- exchanger through gerie silencing in normal rat cholangiocytes. ae2 gene silencing caused a marked inhibition of unstimulated and secretin-stimulated C1-/HC03- exchange. in conclusión, we show that maintenance of the bile acid pool is crucial for secretin to induce bicarbonate-rich choleresis in normal rat, which occurs via a chloride-bicarbonate exchange process consistent with ae2 function.