Download presentation
Presentation is loading. Please wait.
1
Regulation of cholangiocyte bile secretion
Leonardo Baiocchi, Gene LeSage, Shannon Glaser, Gianfranco Alpini Journal of Hepatology Volume 31, Issue 1, Pages (July 1999) DOI: /S (99)
2
Fig. 1 Pure subpopulations of small (a, ∼8 μm in diameter) and large (b, ∼15 μm in diameter) cholangiocytes and small (c, <15 μm in diameter) and large (d, >15 μm in diameter) IBDUs obtained from different portions of the intrahepatic biliary tree. Small and large cholangiocytes were obtained by counterflow elutriation (Reproduced with permission from ref. 10). Small ducts were pruned off from large ducts by a pulsed nitrogen laser beam (Reproduced with permission from ref. 4). Note that small and large cholangiocytes (orig. magn., ×625) and small and large IBDUs (orig. magn., ×2100) differ in size and morphological appearance. Journal of Hepatology , DOI: ( /S (99) )
3
Fig. 2 Schematic representation of the effect of secretin on the cholangiocyte secretion. Secretin interacts with basolateral receptors and increases intracellular cAMP synthesis, which acts via PKA to phosphorylate and activate CFTR. CFTR functions as a Cl− channel. CFTR, a member of the ATP-binding cassette proteins, has two ATP binding sites, and ATP-binding is required for Cl− channel opening. Maintenance of the Cl−/HCO3− exchanger is dependent upon the Cl− channel function of CFTR, presumably due to the requirement for CFTR to return Cl− to the duct lumen that is internalized into cholangiocytes by the Cl−/HCO3− exchanger. Journal of Hepatology , DOI: ( /S (99) )
4
Fig. 3 Cartoon showing the heterogeneity of the secretin and somatostatin (SSTR2) receptor in different-sized (small and large) cholangiocytes along the length of the intrahepatic biliary tree. Note that small cholangiocytes in small ducts do not express the secretin or SSTR2 receptor and do not respond physiologically to either secretin or somatostatin. In contrast, large cholangiocytes contain the SR and respond to secretin with increases in cAMP levels, opening of Cl− channels opening and activation of Cl−/HCO3− exchanger activity. Stimulation of the SSTR2 receptor in large cholangiocytes leads to depressed cAMP synthesis and to a decrease in Cl− channels opening and Cl−/HCO3− exchanger activity. Journal of Hepatology , DOI: ( /S (99) )
5
Fig. 4 (Top) Genetic expression of SSTR2 mRNA in small and large cholangiocytes purified from BDL rats by counterflow elutriation. Note that SSTR2 gene expression is restricted to large cholangiocytes in large bile ducts. (Bottom) Effect of somatostatin on basal and secretin-induced cAMP levels in small and large cholangiocytes from BDL rats. Note that somatostatin induces a decrease in secretin-stimulated cAMP synthesis.* p<0.05 vs.secretin-stimulated cAMP levels. (Reproduced with permission from reference 12). Journal of Hepatology , DOI: ( /S (99) )
6
Fig. 5 Effect of secretin and gastrin on bile secretion (A) and biliary bicarbonate excretion (B) in normal and BDL rats. (A) Hormones were infused for 30 min via jugular vein cannula after a 60-min equilibration period with Krebs-Henseleit bicarbonate solution (KRH).* p< 0.05 vs. its basal value. ▴ p<0.05 vs.secretin-stimulated bile secretion. (B) Bicarbonate concentration was measured as total CO2.). * p< 0.05 vs. its corresponding value from normal rat liver ▴ p<0.05 vs. secretin-stimulated bicarbonate secretion of BDL rats. ** p< 0.05 vs. its basal value. (Reproduced with permission from reference 5). Journal of Hepatology , DOI: ( /S (99) )
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.