Proinflammatory Cytokines Inhibit Secretion in Rat Bile Duct Epithelium

Cholangiocytes absorb and secrete fluid, modifying primary canalicular bile. In several Cl−-secreting epithelia, Na+-K+-2Cl− cotransport is a basolateral Cl− uptake pathway facilitating apical Cl− secretion. To determine if cholangiocytes possess similar mechanisms independent of CO2/HCO[Formula: see text], we assessed Cl−-dependent secretion in rat liver isolated polarized bile duct units (IBDUs) by using videomicroscopy. Without CO2/HCO[Formula: see text], forskolin (FSK) stimulated secretion entirely dependent on Na+ and Cl−and inhibited by Na+-K+-2Cl−inhibitor bumetanide. Carbonic anhydrase inhibitor ethoxyzolamide had no effect on FSK-stimulated secretion, indicating negligible endogenous CO2/HCO[Formula: see text] transport. In contrast, FSK-stimulated secretion was inhibited ∼85% by K+ channel inhibitor Ba2+ and blocked completely by bumetanide plus Ba2+. IBDU Na+-K+-2Cl− cotransport activity was assessed by recording intracellular pH during NH4Cl exposure. Bumetanide inhibited initial acidification rates due to NH[Formula: see text] entry in the presence and absence of CO2/HCO[Formula: see text]. In contrast, when stimulated by FSK, a 35% increase in Na+-K+-2Cl− cotransport activity occurred without CO2/HCO[Formula: see text]. These data suggest a cellular model of HCO[Formula: see text]-independent secretion in which Na+-K+-2Cl−cotransport maintains high intracellular Cl−concentration. Intracellular cAMP concentration increases activate basolateral K+ conductance, raises apical Cl−permeability, and causes transcellular Cl− movement into the lumen. Polarized IBDU cholangiocytes are capable of vectorial Cl−-dependent fluid secretion independent of HCO[Formula: see text]. Bumetanide-sensitive Na+-K+-2Cl− cotransport, Cl−/HCO[Formula: see text] exchange, and Ba2+-sensitive K+ channels are important components of stimulated fluid secretion in intrahepatic bile duct epithelium.

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Permeability characteristics of bile duct in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1982.242.1.g52 ◽

1982 ◽

Vol 242 (1) ◽

pp. G52-G57 ◽

Cited By ~ 3

Author(s):

N. D. Smith ◽

J. L. Boyer

Keyword(s):

Bile Duct ◽

Partition Coefficients ◽

Intercellular Junctions ◽

Ringer Solution ◽

Permeability Barrier ◽

Permeability Characteristics ◽

Duct Epithelium ◽

Bile Duct Epithelium ◽

Rat Bile

To determine the permeability of the bile duct epithelium of the rat to several hydrophilic nonelectrolytes, isolated segments of rat bile duct (1-2 cm) were perfused with Ringer solution in situ. [14C]urea, [14C]erythritol, [14C]sucrose, or [3H]inulin was administered intravenously, and drops of duct perfusate were collected. Perfusate-to-plasma ratios for each solute were inversely related to their molecular weight (MW): inulin [0.13 +/- 0.06 (SD)], sucrose (0.20 +/- 0.08), erythritol (0.32 +/- 0.11), and urea (0.34 +/- 0.13). Permeability coefficients (P) expressed in cm.s-1 X 10(5) were determined for inulin (4.5 +/- 1.5), sucrose (8.5 +/- 2.6), erythritol (12.6 +/- 3.9), and urea (15.8 +/- 1.6). These values vary directly with their respective nonaqueous-aqueous partition coefficients (K) and inversely with their MW. Although P is directly related to K in both olive oil and isobutanol systems, the bile duct behaves as if its permeability barrier is more hydrophilic than isobutanol. These results indicate that the inert solutes urea, erythritol, sucrose, and inulin cross the epithelium of the rat bile duct by a polar route, possibly via intercellular junctions, and that erythritol may not be an ideal marker of canalicular bile flow.

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