Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver. 1998

M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
Liver Study Unit and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. michael.nathanson@yale.edu

Cholestasis is a cardinal complication of liver disease, but most treatments are merely supportive. Here we report that the sulfonylurea glybenclamide potently stimulates bile flow and bicarbonate excretion in the isolated perfused rat liver. Video-microscopic studies of isolated hepatocyte couplets and isolated bile duct segments show that this stimulatory effect occurs at the level of the bile duct epithelium, rather than through hepatocytes. Measurements of cAMP, cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide directly activates Na+-K+-2Cl- cotransport, rather than other transporters or conventional second-messenger systems that link to secretory pathways in these cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced cholestasis show that glybenclamide retains its stimulatory effects on bile flow and bicarbonate excretion even under these conditions. These findings suggest that bile duct epithelia may represent an important new therapeutic target for treatment of cholestatic disorders.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D002779 Cholestasis Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS). Bile Duct Obstruction,Biliary Stasis,Bile Duct Obstructions,Biliary Stases,Cholestases,Duct Obstruction, Bile,Duct Obstructions, Bile,Obstruction, Bile Duct,Obstructions, Bile Duct,Stases, Biliary,Stasis, Biliary
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005905 Glyburide An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D001652 Bile Ducts The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage. Bile Duct,Duct, Bile,Ducts, Bile
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic

Related Publications

M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
April 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
November 1989, Gastroenterology,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
March 1993, Gastroenterology,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
March 2001, Experimental & molecular medicine,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
May 2017, Journal of ethnopharmacology,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
January 2001, Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
November 2015, BMC systems biology,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
April 1999, European journal of medical research,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
August 2001, Gastroenterology,
M H Nathanson, and A D Burgstahler, and A Mennone, and J A Dranoff, and L Rios-Velez
July 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Copied contents to your clipboard!