Somatostatin inhibits secretin-induced ductal hyper choleresis and exocytosis by cholangiocytes after bile duct ligation in the rat. Tietz, Pamela S., Gianfranco Alpini, Linh D. Pham, Nicholas F. Larusso. Center for Basic Research in Digestive Diseases, Mayo Medical School, Clinic, and Foundation, Rochester, MN 55905
APStracts 2:0036G, 1995.
Previous work from our laboratory has implicated hormone-induced, plasma membrane movement (i.e., endo- and exocytosis) in water and electrolyte transport by the epithelial cells that line the ducts in the liver (i.e., cholangiocytes). To further explore the cellular mechanisms regulating ductal bile secretion, we infused somatostatin and/or secretin intravenously into rats two weeks after either bile duct ligation (BDL), a procedure which induces selective proliferation of cholangiocytes, or sham surgery, and measured bile flow and biliary constituents. We also determined the effect of somatostatin on basal and secretin-induced exocytosis by purified cholangiocytes isolated from rat liver after BDL. Finally, we studied the expression of the somatostatin receptor gene by both RNase protection and nuclear run-on assays using cDNA's encoding for two subtypes of the somatostatin receptor gene (i.e., SSTR1 and SSTR2). In vivo, somatostatin infusion caused a dose-dependent, bicarbonate -poor decrease (57% maximal decrease below baseline; p<0.05) in bile flow in BDL but not in sham operated rats; in contrast, secretin caused a dose-dependent, bicarbonate-rich choleresis (228% maximal increase above baseline; p<0.05) in BDL but not in sham operated rats. Simultaneous or prior infusion of somatostatin inhibited the secretin-induced hypercholeresis in BDL rats. In vitro, somatostatin had no effect on basal exocytosis by cholangiocytes isolated from BDL rats; however, somatostatin inhibited (88% maximal inhibition; p<0.05) secretin-induced exocytosis by cholangiocytes in a dose -dependent fashion. In addition, somatostatin inhibited secretin -induced increases in levels of cyclic AMP in cholangiocytes isolated from BDL rats. By RNase protection assays, SSTR2 (but not SSTR1) mRNA was detected in normal liver exclusively in cholangiocytes; after BDL, SSTR2 mRNA expression increased nearly equal to 20-fold per cholangiocyte as compared to normal rats. Synthesis of SSTR2 mRNA, as assessed by nuclear run-on assays, increased to a similar extent in individual cholangiocytes following BDL. Our data suggest that somatostatin interacts directly with receptors located in liver exclusively on cholangiocytes and, in concert with secretin, regulates ductal bile secretion in BDL rat liver via alterations in cyclic AMP-dependent exocytosis. 

Received 30 June 1994; accepted in final form 25 February 1995.
APS Manuscript Number G253-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.