Hormonal Regulation of Cholangiocyte Secretion

Cholangiocyte bicarbonate secretion is highly regulated by hormones, peptides and nerves since it contributes significantly to the total bicarbonate requirement for digestive functions and is the major determinant of alkalinity and hydration of hepatic bile. During digestion secretin induces a ductular bicarbonate-rich choleresis by activation of apical Cl⁻¹ HCO₃ ⁻ exchanger via a cAMP and PKA-dependent pathway. In the post-prandial phase, when the parasympathetic system predominates, acetylcholine, by activation of calcineurin, induces a “sensitization” of adenylyl cyclase to secretin, leading to a maximal stimulation of the C17 HCO₃ ⁻ exchanger. Similar to secretin, vasoactive intestinal peptide (VIP) and bombesin stimulate cholangiocyte bicarbonate secretion, presumably via a cAMP and cGMP-independent pathway. In contrast, somatostatin, gastrin and insulin exert inhibitory effects on both basal and hormonal induced bicarbonate cholangiocyte secretion. Estrogens, in addition to sustaining cholangiocyte proliferation, play an important role in the modulation of cholangiocyte secretion. Finally corticosteroids stimulate bicarbonate excretion by enhanced expression of cholangiocyte apical Cl⁻/HCO₃ ⁻ exchanger and basolateral Na⁺/H⁺ exchanger.