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Abstract
We have shown that agonist-regulated ductal secretion is limited to large cholangiocytes.
To directly study cholangiocyte heterogeneity along the length of the normal biliary
tree, we defined the genetic and functional expression of agonist-induced ductal secretion
in intrahepatic bile duct units (IBDU) of different sizes. Small IBDU (< 15-microns
diam) were separated from large IBDU (> or = 15-microns diam), and then ducts of different
sizes were characterized by morphometric analysis, gene expression, secretin-induced
adenosine 3',5'-cyclic monophosphate (cAMP) synthesis, and secretion by change in
luminal size in response to agonists. IBDU diameters ranged from 11 to 65 microns.
Secretin increased ductal secretion solely in large IBDU. Forskolin induced a modest
increase in ductal secretion in small IBDU but markedly increased ductal secretion
in large IBDU. Secretion increased Cl-/HCO3- exchanger activity and cAMP levels in
large but not small IBDU. Secretin receptor and Cl-/HCO3 exchanger mRNAs were detected
only in large IBDU. We propose that agonist-induced ductal secretion occurs in large
(> or = 15-microns diam) but not small (< 15-microns diam) intrahepatic ducts.