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Article: Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones. Studies in the prairie dog

TitleRole of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones. Studies in the prairie dog
Authors
Issue Date1981
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 1981, v. 67 n. 6, p. 1712-1723 How to Cite?
AbstractBecause mucin glycoproteins may be important in the pathophysiology of gallstones, we studied the relationship among biliary lipids, gallbladder mucin secretion, and gallstone formation in cholesterol-fed prairie dogs. Organ culture studies of gallbladder explants revealed that the incorporation of [3H]glucosamine into tissue and secretory gallbladder glycoproteins was significantly increased at 3, 5, 8, and 14 d of feeding. Peak secretion of labeled mucin occurred at 5 d, when total tissue and secreted glycoprotein production was fivefold greater than control. Gel filtration of the secreted glycoprotein on Sepharose 4B indicated that the majority of radio-activity was present in a macromolecule of >1 million molecular weight. The increased secretion of gallbladder mucin was organ specific, in that [3H]-glucosamine incorporation into glycoproteins of stomach and colon was unaffected by cholesterol feeding. Similarly, the incorporation of [3H]mannose into gallbladder membrane glycoproteins was not altered by cholesterol feeding. The rate of glycoprotein synthesis and secretion returned to normal upon withdrawal of the cholesterol diet, and ligation of the cystic duct before cholesterol feeding prevented gallbladder mucin hypersecretion. Both results indicate that the stimulus to mucin secretion was a constituent of bile. Gallbladder bile after 5 d contained cholesterol in micelles, liquid crystals, and crystals, whereas hepatic bile remained a single micellar phase throughout cholesterol feeding. For this reason the cholesterol-saturation indices of gallbladder bile were compared in both homogenized and centrifuged samples. The micellar phase of gallbladder bile was appreciably less saturated than homogenized bile at 5 and 8 d, which reflects the continuous nucleation of cholesterol in the gallbladder. Purified human gallbladder mucin gels were shown to induce nucleation of lecithin-cholesterol liquid crystals from supersaturated hepatic bile. These in turn gave rise to cholesterol monohydrate crystals within 18 h. Control super-saturated hepatic bile could not be nucleated by the addition of other proteins, and was stable for days upon standing. These results suggest that the increase in cholesterol content of bile in cholesterol-fed prairie dogs stimulates gallbladder mucus hyper-secretion, and that gallbladder mucus gel is a nucleating agent for biliary cholesterol.
Persistent Identifierhttp://hdl.handle.net/10722/175617
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, SPen_US
dc.contributor.authorLa Mont, JTen_US
dc.contributor.authorCarey, MCen_US
dc.date.accessioned2012-11-26T09:00:09Z-
dc.date.available2012-11-26T09:00:09Z-
dc.date.issued1981en_US
dc.identifier.citationJournal Of Clinical Investigation, 1981, v. 67 n. 6, p. 1712-1723en_US
dc.identifier.issn0021-9738en_US
dc.identifier.urihttp://hdl.handle.net/10722/175617-
dc.description.abstractBecause mucin glycoproteins may be important in the pathophysiology of gallstones, we studied the relationship among biliary lipids, gallbladder mucin secretion, and gallstone formation in cholesterol-fed prairie dogs. Organ culture studies of gallbladder explants revealed that the incorporation of [3H]glucosamine into tissue and secretory gallbladder glycoproteins was significantly increased at 3, 5, 8, and 14 d of feeding. Peak secretion of labeled mucin occurred at 5 d, when total tissue and secreted glycoprotein production was fivefold greater than control. Gel filtration of the secreted glycoprotein on Sepharose 4B indicated that the majority of radio-activity was present in a macromolecule of >1 million molecular weight. The increased secretion of gallbladder mucin was organ specific, in that [3H]-glucosamine incorporation into glycoproteins of stomach and colon was unaffected by cholesterol feeding. Similarly, the incorporation of [3H]mannose into gallbladder membrane glycoproteins was not altered by cholesterol feeding. The rate of glycoprotein synthesis and secretion returned to normal upon withdrawal of the cholesterol diet, and ligation of the cystic duct before cholesterol feeding prevented gallbladder mucin hypersecretion. Both results indicate that the stimulus to mucin secretion was a constituent of bile. Gallbladder bile after 5 d contained cholesterol in micelles, liquid crystals, and crystals, whereas hepatic bile remained a single micellar phase throughout cholesterol feeding. For this reason the cholesterol-saturation indices of gallbladder bile were compared in both homogenized and centrifuged samples. The micellar phase of gallbladder bile was appreciably less saturated than homogenized bile at 5 and 8 d, which reflects the continuous nucleation of cholesterol in the gallbladder. Purified human gallbladder mucin gels were shown to induce nucleation of lecithin-cholesterol liquid crystals from supersaturated hepatic bile. These in turn gave rise to cholesterol monohydrate crystals within 18 h. Control super-saturated hepatic bile could not be nucleated by the addition of other proteins, and was stable for days upon standing. These results suggest that the increase in cholesterol content of bile in cholesterol-fed prairie dogs stimulates gallbladder mucus hyper-secretion, and that gallbladder mucus gel is a nucleating agent for biliary cholesterol.en_US
dc.languageengen_US
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_US
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBile - Analysisen_US
dc.subject.meshCholelithiasis - Etiologyen_US
dc.subject.meshCholesterol, Dietary - Administration & Dosageen_US
dc.subject.meshChromatographyen_US
dc.subject.meshDogsen_US
dc.subject.meshGallbladder - Pathology - Secretionen_US
dc.subject.meshGlucosamine - Pharmacologyen_US
dc.subject.meshGlycoproteins - Analysis - Biosynthesisen_US
dc.subject.meshLipids - Analysisen_US
dc.subject.meshMucus - Metabolismen_US
dc.subject.meshOrgan Culture Techniquesen_US
dc.subject.meshTime Factorsen_US
dc.titleRole of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones. Studies in the prairie dogen_US
dc.typeArticleen_US
dc.identifier.emailLee, SP: sumlee@hku.hken_US
dc.identifier.authorityLee, SP=rp01351en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1172/JCI110209-
dc.identifier.pmid7240416-
dc.identifier.scopuseid_2-s2.0-0019419074en_US
dc.identifier.volume67en_US
dc.identifier.issue6en_US
dc.identifier.spage1712en_US
dc.identifier.epage1723en_US
dc.identifier.isiWOS:A1981LT89400017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLee, SP=7601417497en_US
dc.identifier.scopusauthoridLa Mont, JT=6507274060en_US
dc.identifier.scopusauthoridCarey, MC=7202744540en_US

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