Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct–ligated rats

Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes

“…Other factors that may modulate cholangiocyte growth in BDL rats include growth factors (e.g., hepatocyte growth factor, epidermal growth factor, transforming growth factor-␤, and insulinlike growth factor). 32 Parasympathetic innervation is required for cholangiocyte growth, 20 and interruption of dopaminergic innervation inhibits cholangiocyte proliferation in BDL rats. 33 Gastrin and somatostatin have been shown to inhibit both hyperplastic and neoplastic growth in rat cholangiocytes and human cholangiocarcinoma cell lines.…”

“…Two pure (by ␥-GT histochemistry) subpopulations of small and large cholangiocytes were purified from normal rats and rats fed for 1 week 1% TC, 1% TLC, or control diet by counterflow elutriation followed by immunoaffinity separation 3,4,6,7,9,19,20 using a monoclonal antibody against an unidentified antigen expressed by all intrahepatic cholangiocytes. 19 Cell viability (approximately 97%) was determined by trypan blue exclusion.…”

“…Morphometry of frozen liver sections (5 m thick, n ϭ 3 for each group) was performed by point count analysis 7,22 by determining the number of small (Ͻ15 m in diameter 23 ) and large (Ͼ15 m in diameter 23 ) ducts stained for CK-19. 6,7 This technique has been previously used by us 6,7,9,20 to measure intrahepatic ductal mass in both normal and rat livers with ductal hyperplasia. Following staining for CK-19, 6,7 sections were counterstained with hematoxylin and examined in a coded fashion with an Olympus BX 40 microscope (Olympus Optical Co., Ltd., Tokyo, Japan).…”

H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway

“…66 Maintenance of cAMP levels by the administration of forskolin or b1-and b2-adrenergic receptor agonists prevents the stimulatory effects of cholinergic or adrenergic denervation, respectively, on cholangiocyte apoptosis. 34,65 Furthermore, upregulation of the cAMP system (by chronic forskolin administration) alone is sufficient to induce cholangiocyte hyperplasia in normal rats, similar to the BDL rat model. 5 Our study shows that chronic administration of the H3R agonist, RAMH to BDL rats induced a decrease in cholangiocyte cAMP levels compared to cAMP levels of cholangiocytes from BDL rats treated with NaCl.…”

“…# Po0.05 vs corresponding value from BDL rats treated with RAMH. Histamine regulation of cholangiocyte growth H Francis et al increased cholangiocyte growth is closely coupled with enhanced cAMP levels, 5,39,65 whereas reduced cholangiocyte proliferation is associated with decreased cAMP levels. 66 Maintenance of cAMP levels by the administration of forskolin or b1-and b2-adrenergic receptor agonists prevents the stimulatory effects of cholinergic or adrenergic denervation, respectively, on cholangiocyte apoptosis.…”