Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes

Background & Aims: Vasoactive intestinal polypeptide (VIP) is a neuropeptide with diverse biological functions including stimulatory effects on bile secretion. The effects of VIP on bile secretion and its site of action were examined. Methods: Choleretic effects of VIP were examined using isolat...

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Veröffentlicht in:Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 1999-08, Vol.117 (2), p.420-428
Hauptverfasser: Cho, Won Kyoo, Boyer, James L.
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Boyer, James L.
description Background & Aims: Vasoactive intestinal polypeptide (VIP) is a neuropeptide with diverse biological functions including stimulatory effects on bile secretion. The effects of VIP on bile secretion and its site of action were examined. Methods: Choleretic effects of VIP were examined using isolated perfused livers, hepatocyte couplets, isolated bile duct units, and cholangiocytes from rat liver. Results: VIP (100 nmol/L) produced a small increase in bile flow and bile salt output in taurocholate-supplemented isolated perfused livers but had no significant effect on bile flow in the absence of bile salt supplements or on fluid secretion in isolated hepatocyte couplets. In addition, VIP significantly increased bile pH, bicarbonate concentration, and output in the isolated perfused livers from both normal and 2 week bile duct–ligated rats, although bile flow increased only in the bile duct–ligated model. VIP also produced a dose-dependent increase in fluid secretion in isolated bile duct units, which was inhibited significantly by VIP antagonist, a specific VIP receptor inhibitor. This VIP-stimulated secretory response in isolated bile duct units was more potent than those produced by bombesin or secretin. Neither somatostatin nor substance P inhibited the VIP response in isolated bile duct units. In contrast to secretin, VIP had no significant effect on adenosine 3',5'-cyclic monophosphate (cAMP) levels in isolated cholangiocytes. Conclusions: VIP is a potent stimulant of fluid and bicarbonate secretion from cholangiocytes via cAMP-independent pathways, suggesting that this neuropeptide plays a major regulatory role in biliary transport and secretion.
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The effects of VIP on bile secretion and its site of action were examined. Methods: Choleretic effects of VIP were examined using isolated perfused livers, hepatocyte couplets, isolated bile duct units, and cholangiocytes from rat liver. Results: VIP (100 nmol/L) produced a small increase in bile flow and bile salt output in taurocholate-supplemented isolated perfused livers but had no significant effect on bile flow in the absence of bile salt supplements or on fluid secretion in isolated hepatocyte couplets. In addition, VIP significantly increased bile pH, bicarbonate concentration, and output in the isolated perfused livers from both normal and 2 week bile duct–ligated rats, although bile flow increased only in the bile duct–ligated model. VIP also produced a dose-dependent increase in fluid secretion in isolated bile duct units, which was inhibited significantly by VIP antagonist, a specific VIP receptor inhibitor. This VIP-stimulated secretory response in isolated bile duct units was more potent than those produced by bombesin or secretin. Neither somatostatin nor substance P inhibited the VIP response in isolated bile duct units. In contrast to secretin, VIP had no significant effect on adenosine 3',5'-cyclic monophosphate (cAMP) levels in isolated cholangiocytes. Conclusions: VIP is a potent stimulant of fluid and bicarbonate secretion from cholangiocytes via cAMP-independent pathways, suggesting that this neuropeptide plays a major regulatory role in biliary transport and secretion.</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/gast.1999.0029900420</identifier><identifier>PMID: 10419925</identifier><identifier>CODEN: GASTAB</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Bile - metabolism ; Bile Ducts - cytology ; Bile Ducts - drug effects ; Bile Ducts - metabolism ; Biological and medical sciences ; Cyclic AMP - physiology ; Dose-Response Relationship, Drug ; Fundamental and applied biological sciences. Psychology ; Liver. Bile. 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The effects of VIP on bile secretion and its site of action were examined. Methods: Choleretic effects of VIP were examined using isolated perfused livers, hepatocyte couplets, isolated bile duct units, and cholangiocytes from rat liver. Results: VIP (100 nmol/L) produced a small increase in bile flow and bile salt output in taurocholate-supplemented isolated perfused livers but had no significant effect on bile flow in the absence of bile salt supplements or on fluid secretion in isolated hepatocyte couplets. In addition, VIP significantly increased bile pH, bicarbonate concentration, and output in the isolated perfused livers from both normal and 2 week bile duct–ligated rats, although bile flow increased only in the bile duct–ligated model. VIP also produced a dose-dependent increase in fluid secretion in isolated bile duct units, which was inhibited significantly by VIP antagonist, a specific VIP receptor inhibitor. This VIP-stimulated secretory response in isolated bile duct units was more potent than those produced by bombesin or secretin. Neither somatostatin nor substance P inhibited the VIP response in isolated bile duct units. In contrast to secretin, VIP had no significant effect on adenosine 3',5'-cyclic monophosphate (cAMP) levels in isolated cholangiocytes. 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Psychology</topic><topic>Liver. Bile. Biliary tracts</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Perfusion</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Vasoactive Intestinal Peptide - drug effects</topic><topic>Receptors, Vasoactive Intestinal Peptide - physiology</topic><topic>Vasoactive Intestinal Peptide - pharmacology</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cho, Won Kyoo</creatorcontrib><creatorcontrib>Boyer, James L.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Won Kyoo</au><au>Boyer, James L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>117</volume><issue>2</issue><spage>420</spage><epage>428</epage><pages>420-428</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><coden>GASTAB</coden><abstract>Background &amp; Aims: Vasoactive intestinal polypeptide (VIP) is a neuropeptide with diverse biological functions including stimulatory effects on bile secretion. The effects of VIP on bile secretion and its site of action were examined. Methods: Choleretic effects of VIP were examined using isolated perfused livers, hepatocyte couplets, isolated bile duct units, and cholangiocytes from rat liver. Results: VIP (100 nmol/L) produced a small increase in bile flow and bile salt output in taurocholate-supplemented isolated perfused livers but had no significant effect on bile flow in the absence of bile salt supplements or on fluid secretion in isolated hepatocyte couplets. In addition, VIP significantly increased bile pH, bicarbonate concentration, and output in the isolated perfused livers from both normal and 2 week bile duct–ligated rats, although bile flow increased only in the bile duct–ligated model. VIP also produced a dose-dependent increase in fluid secretion in isolated bile duct units, which was inhibited significantly by VIP antagonist, a specific VIP receptor inhibitor. This VIP-stimulated secretory response in isolated bile duct units was more potent than those produced by bombesin or secretin. Neither somatostatin nor substance P inhibited the VIP response in isolated bile duct units. In contrast to secretin, VIP had no significant effect on adenosine 3',5'-cyclic monophosphate (cAMP) levels in isolated cholangiocytes. Conclusions: VIP is a potent stimulant of fluid and bicarbonate secretion from cholangiocytes via cAMP-independent pathways, suggesting that this neuropeptide plays a major regulatory role in biliary transport and secretion.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10419925</pmid><doi>10.1053/gast.1999.0029900420</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection
subjects Amino Acid Sequence
Animals
Bile - metabolism
Bile Ducts - cytology
Bile Ducts - drug effects
Bile Ducts - metabolism
Biological and medical sciences
Cyclic AMP - physiology
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Liver. Bile. Biliary tracts
Male
Molecular Sequence Data
Perfusion
Rats
Rats, Sprague-Dawley
Receptors, Vasoactive Intestinal Peptide - drug effects
Receptors, Vasoactive Intestinal Peptide - physiology
Vasoactive Intestinal Peptide - pharmacology
Vertebrates: digestive system
title Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes
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