Hormonal regulation of bicarbonate secretion in the biliary epithelium

Bicarbonate excretion in bile is a major function of the biliary epithelium. it is driven by the apically located Cl(-)/HCO(3)(-) exchanger which is functionally coupled with a cAMP-dependent Cl(-) channel (CFTR). A number of hormones and/or neuropeptides with different mechanisms and at different intracellular levels regulate, in concert, the processes underlying bicarbonate excretion in the biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating the activity of the Cl-/HCO(3)(-) exchanger by cAMP and protein kinase A mediated phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved in the run-down of secretory stimulus after secretin removal. Acetylchorine potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal peptide also enhance the Cl(-)/HCO(3)(-) exchanger activity, but the intracellular signal transduction pathway has not yet been defined. Somatostatin and gastrin inhibit basal and/or secretin-stimulated bicarbonate excretion by downregulating the secretin receptor and decreasing cAMP intracellular levels induced by secretin.