AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 5 1064-G1074, Copyright © 1997 by American Physiological Society

ARTICLES

Large but not small intrahepatic bile ducts are involved in secretin-regulated ductal bile secretion

G. Alpini, S. Glaser, W. Robertson, R. E. Rodgers, J. L. Phinizy, J. Lasater and G. D. LeSage
Department of Internal Medicine, Scott and White Hospital, Temple, Texas, USA.

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.

This article has been cited by other articles:

				H. Francis, S. Glaser, S. DeMorrow, E. Gaudio, Y. Ueno, J. Venter, D. Dostal, P. Onori, A. Franchitto, M. Marzioni, et al. Small mouse cholangiocytes proliferate in response to H1 histamine receptor stimulation by activation of the IP3/CaMK I/CREB pathway Am J Physiol Cell Physiol, August 1, 2008; 295(2): C499 - C513. [Abstract] [Full Text] [PDF]

				H. Francis, G. LeSage, S. DeMorrow, D. Alvaro, Y. Ueno, J. Venter, S. Glaser, M. G. Mancino, L. Marucci, A. Benedetti, et al. The {alpha}2-adrenergic receptor agonist UK 14,304 inhibits secretin-stimulated ductal secretion by downregulation of the cAMP system in bile duct-ligated rats Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1252 - C1262. [Abstract] [Full Text] [PDF]

				G. Alpini, J. L. Phinizy, S. Glaser, H. Francis, A. Benedetti, L. Marucci, and G. LeSage Development and characterization of secretin-stimulated secretion of cultured rat cholangiocytes Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G1066 - G1073. [Abstract] [Full Text] [PDF]

				A.-Y. Gong, P. S. Tietz, M. A. Muff, P. L. Splinter, R. C. Huebert, M. Z. Strowski, X.-M. Chen, and N. F. LaRusso Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytes Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1205 - C1214. [Abstract] [Full Text] [PDF]

				S. Glaser, D. Alvaro, T. Roskams, J. L. Phinizy, G. Stoica, H. Francis, Y. Ueno, B. Barbaro, M. Marzioni, J. Mauldin, et al. Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G683 - G694. [Abstract] [Full Text] [PDF]

				L. Marucci, G. Alpini, S. S. Glaser, D. Alvaro, A. Benedetti, H. Francis, J. L. Phinizy, M. Marzioni, J. Mauldin, J. Venter, et al. Taurocholate feeding prevents CCl4-induced damage of large cholangiocytes through PI3-kinase-dependent mechanism Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G290 - G301. [Abstract] [Full Text] [PDF]

				N. Kanno, G. LeSage, S. Glaser, and G. Alpini Regulation of cholangiocyte bicarbonate secretion Am J Physiol Gastrointest Liver Physiol, September 1, 2001; 281(3): G612 - G625. [Abstract] [Full Text] [PDF]

				S. K. Singh, A. Mennone, A. Gigliozzi, F. Fraioli, and J. L. Boyer Cl{-}-dependent secretory mechanisms in isolated rat bile duct epithelial units Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G438 - G446. [Abstract] [Full Text] [PDF]

				G. Lesage, S. Glaser, Y. Ueno, D. Alvaro, L. Baiocchi, N. Kanno, J. L. Phinizy, H. Francis, and G. Alpini Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G182 - G190. [Abstract] [Full Text] [PDF]

				T. V. Masyuk, E. L. Ritman, and N. F. LaRusso Quantitative Assessment of the Rat Intrahepatic Biliary System by Three-Dimensional Reconstruction Am. J. Pathol., June 1, 2001; 158(6): 2079 - 2088. [Abstract] [Full Text] [PDF]

				J. M. McGill, M. S. Yen, O. W. Cummings, G. Alpini, G. LeSage, K. E. Pollok, B. Miller, S. K. Engle, and A. P. Stansfield Interleukin-5 inhibition of biliary cell chloride currents and bile flow Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G738 - G745. [Abstract] [Full Text] [PDF]

				G. D. LeSage, S. S. Glaser, L. Marucci, A. Benedetti, J. L. Phinizy, R. Rodgers, A. Caligiuri, E. Papa, Z. Tretjak, A.-M. Jezequel, et al. Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver Am J Physiol Gastrointest Liver Physiol, May 1, 1999; 276(5): G1289 - G1301. [Abstract] [Full Text] [PDF]

				A. Caligiuri, S. Glaser, R. E. Rodgers, J. L. Phinizy, W. Robertson, E. Papa, M. Pinzani, and G. Alpini Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes Am J Physiol Gastrointest Liver Physiol, October 1, 1998; 275(4): G835 - G846. [Abstract] [Full Text] [PDF]