{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T15:00:56Z","timestamp":1765638056603,"version":"3.48.0"},"reference-count":26,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1992,8]]},"abstract":"<jats:p>Aspirin, which inhibits mucin secretion in the gastrointestinal tract prevents gall stone formation in animals and may reduce gall stone recurrence in man. This study examines the effect of aspirin on mucin synthesis in human gall bladder explants. Two hundred explants were cultured with 3H-glucosamine (74 kBq\/ml) for 24 hours at 37 degrees C. Mucin and other glycoproteins were isolated by papain digestion (72 hours) and exhaustive dialysis (144 hours) to remove non-incorporated radioactivity and digested protein. 3H-glucosamine was readily incorporated into glycoprotein. Pooled gall bladder explants were fractionated on a CsCl density gradient and by gel filtration on Sepharose 2B and 4B to confirm that &gt;90% radioactivity was incorporated into mucin. Acetylsalicylic acid (230-666 micrograms\/ml) significantly reduced total 3H-glucosamine incorporation (43-89%), p&lt;0.01 (unpaired t test). Diclofenac (125-1250 micrograms\/ml), similarly reduced incorporation by 45-97% p&lt;0.001 (unpaired t test). Inhibition of mucin glycoprotein biosynthesis was irreversible with both drugs. Analysis of pooled samples on Sepharose 4B showed abolition of radioactive incorporation into mucin but no effect on incorporation into low molecular weight glycoprotein material (10% of total incorporation). This study provides a method for measuring human gall bladder mucin synthesis and shows its irreversible inhibition by acetylsalicylic acid and diclofenac at concentrations compatible with a therapeutic dose.<\/jats:p>","DOI":"10.1136\/gut.33.8.1109","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"1109-1112","source":"Crossref","is-referenced-by-count":20,"title":["Mucus glycoprotein biosynthesis in the human gall bladder: inhibition by aspirin."],"prefix":"10.1136","volume":"33","author":[{"given":"M","family":"Rhodes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Allen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T W","family":"Lennard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1992,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1097\/00000658-196305000-00002","article-title":"The anatomy of gallstones","volume":"157","author":"Womack, N.; Zeppa, R.; Irvin, G.","year":"1963","unstructured":"Womack N, Zeppa R, Irvin G. The anatomy of gallstones. Ann Surg 1963; 157: 670-86.","journal-title":"Ann Surg"},{"key":"ref_2","first-page":"846","article-title":"Role of sulphated glycoprotein in gallstone formation","volume":"132","author":"Maki, T.; Matsushiro, T.; Susuki, N.; Nakamura, N.","year":"1971","unstructured":"Maki T, Matsushiro T, Susuki N, Nakamura N. Role of sulphated glycoprotein in gallstone formation. Surg Gynecol Obstet 1971; 132: 846-51.","journal-title":"Surg Gynecol Obstet"},{"key":"ref_3","first-page":"707","article-title":"Bovine gallbladder mucin binds bilirubin","volume-title":"vitro. Gastroenterology 1983; 85","author":"Smith, B.F.; LaMont, J.T.","unstructured":"Smith BF, LaMont JT. Bovine gallbladder mucin binds bilirubin in vitro. Gastroenterology 1983; 85: 707-12."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/path.1711340304","article-title":"Hypersecretion of mucus glycoproteins by gallbladder epithelium in experimental cholelithiasis","volume":"134","author":"Lee, S.P.","year":"1981","unstructured":"Lee SP. Hypersecretion of mucus glycoproteins by gallbladder epithelium in experimental cholelithiasis. J Pathol 1981; 134: 199-207.","journal-title":"J Pathol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0002-9610(83)90166-6","article-title":"Role of gallbladder mucus in the pathogenesis of cholesterol gallstones","volume":"145","author":"Doty, J.E.; Pitt, H.A.; Kuchenbecker, S.L.; Porter-Fink, V.; Den Besten, L.W.","year":"1983","unstructured":"Doty JE, Pitt HA, Kuchenbecker SL, Porter-Fink V, Den Besten LW. Role of gallbladder mucus in the pathogenesis of cholesterol gallstones. AmJ Surg 1983; 145: 54-60.","journal-title":"AmJ Surg"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000199410","article-title":"Mucus glycoprotein content of human cholesterol gallstones","volume":"36","author":"Pearson, J.P.; Foster, S.N.E.","year":"1987","unstructured":"Pearson JP, Foster SNE. Mucus glycoprotein content of human cholesterol gallstones. Digestion 1987; 36: 132-40.","journal-title":"Digestion"},{"key":"ref_7","first-page":"343","article-title":"Mucous substances and viscosity of normal","volume-title":"and pathological human bile. Gastroenterology 1965","volume":"49","author":"Bouchier, I.A.D.; Cooperband, SR, ElKodsi; B.M.","unstructured":"Bouchier IAD, Cooperband SR, ElKodsi BM. Mucous substances and viscosity of normal and pathological human bile. Gastroenterology 1965; 49: 343-53."},{"key":"ref_8","first-page":"670","article-title":"Biliary mucous substances","volume-title":"dihydrocholesterol-induced cholelithiasis. Gastroenterology 1969; 57","author":"Freston, J.W.; Bouchier, I.A.D.; Newman, J.","unstructured":"Freston JW, Bouchier IAD, Newman J. Biliary mucous substances in dihydrocholesterol-induced cholelithiasis. Gastroenterology 1969; 57: 670-8."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.7466399","article-title":"Aspirin prevention of cholesterol gallstone formation in prairie dogs","volume":"211","author":"Lee, S.P.; Carey, M.C.; LaMont, J.T.","year":"1981","unstructured":"Lee SP, Carey MC, LaMont JT. Aspirin prevention of cholesterol gallstone formation in prairie dogs. Science 1981; 211: 1429-31.","journal-title":"Science"},{"key":"ref_10","first-page":"92","article-title":"Arachidonic acid stimulates mucin secretion in prairie dog gallbladder","volume":"245","author":"LaMont, J.T.; Turner, B.S.; DiBenedetto, D.; Hadin, R.; Schafer, A.I.","year":"1983","unstructured":"LaMont JT, Turner BS, DiBenedetto D, Hadin R, Schafer AI. Arachidonic acid stimulates mucin secretion in prairie dog gallbladder. AmJ7 Physiol 1983; 245: G92-8.","journal-title":"AmJ7 Physiol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1056\/NEJM198812153192403","article-title":"The effects of ursodeoxycholic acid and aspirin on the formation of lithogenic bile and gallstones during loss of weight","volume":"319","author":"Broomfield, P.H.; Chopra, R.; Sheinbaum, R.C.; Bonoris, G.C.; Silverman, A.; Schoenfield, L.J.","year":"1988","unstructured":"Broomfield PH, Chopra R, Sheinbaum RC, Bonoris GC, Silverman A, Schoenfield LJ, et al. The effects of ursodeoxycholic acid and aspirin on the formation of lithogenic bile and gallstones during loss of weight. N EnglJ Med 1988; 319: 1567-72.","journal-title":"N EnglJ Med"},{"key":"ref_12","first-page":"1223","article-title":"Prevention of gallstone recurrence by non-steroidal anti-inflammatory drugs","volume":"ii:","author":"Hood, K.; Gleeson, D.; Ruppin, D.C.; Dowling, R.H.","year":"1988","unstructured":"Hood K, Gleeson D, Ruppin DC, Dowling RH. Prevention of gallstone recurrence by non-steroidal anti-inflammatory drugs. Lancet 1988; ii: 1223-5.","journal-title":"Lancet"},{"key":"ref_13","first-page":"807","article-title":"The potent pronucleating proteins in gallbladder bile of cholesterol gallstone patients are polymeric immunoglobulins","volume":"100","author":"Upadhya, G.A.; Harvey, P.R.C.; Strasberg, S.M.","year":"1991","unstructured":"Upadhya GA, Harvey PRC, Strasberg SM. The potent pronucleating proteins in gallbladder bile of cholesterol gallstone patients are polymeric immunoglobulins. Gastroenterology 1991; 100: A807.","journal-title":"Gastroenterology"},{"key":"ref_14","article-title":"Studies on mucus biosynthesis in the gastrointestinal tract","author":"Hunter, A.C.; Allen, A.; Garner, A.","year":"1989","unstructured":"Hunter AC, Allen A, Garner A. Studies on mucus biosynthesis in the gastrointestinal tract. In: Chantler E, Ratcliffe NA, eds. Mucus and related topics. Society for Experimental Biology, 1989. London & Sydney.","journal-title":"Society for Experimental Biology; related topics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1136\/gut.24.9.812","article-title":"In vitro model for assessment of luminal factors in rectal mucosa","volume":"24","author":"Allan, A.; Jewell, D.P.","year":"1983","unstructured":"Allan A, Jewell DP. In vitro model for assessment of luminal factors in rectal mucosa. Gut 1983; 24: 812-7.","journal-title":"Gut"},{"key":"ref_16","first-page":"359","article-title":"Gastrointestinal mucus. Handbook ofphysiology vol II1","author":"Allen, A.","year":"1989","unstructured":"Allen A. Gastrointestinal mucus. Handbook ofphysiology vol II1. Bethesda, USA: American Physiological Society, 1989: 359-82."},{"key":"ref_17","first-page":"221","article-title":"The composition and polymeric structure of mucus glycoprotein from human gallbladder bile","volume":"706","author":"Pearson, J.P.; Kaura, R.; Taylor, W.; Allen, A.","year":"1982","unstructured":"Pearson JP, Kaura R, Taylor W, Allen A. The composition and polymeric structure of mucus glycoprotein from human gallbladder bile. Biochem Biophys Acta 1982; 706: 221-8.","journal-title":"Biochem Biophys Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1042\/bst0060607","article-title":"A colorimetric assay for glycoproteins based on the periodic acid\/Schiff reaction","volume":"6","author":"Mantle, M.; Allen, A.","year":"1978","unstructured":"Mantle M, Allen A. A colorimetric assay for glycoproteins based on the periodic acid\/Schiff reaction. Biochem Soc Trans 1978; 6: 607-9.","journal-title":"Biochem Soc Trans"},{"key":"ref_19","first-page":"975","article-title":"Gastrointestinal mucus - synthesis, secretion and function","volume-title":"ofthe gastrointestinal tract. Vol 3","author":"Neutra, M.R.; Forster, J.F.","year":"1987","unstructured":"Neutra MR, Forster JF. Gastrointestinal mucus - synthesis, secretion and function. In: Johnson LR, ed. Physiology ofthe gastrointestinal tract. Vol 3. New York: Raven Press, 1987: 975-1009."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1042\/bj1060645","article-title":"The biosynthesis of intestinal mucins. The effect of salicylate on glycoprotein biosynthesis by sheep colonic and human gastric mucosal tissues in vitro","volume":"106","author":"Kent, P.W.; Allen, A.","year":"1968","unstructured":"Kent PW, Allen A. The biosynthesis of intestinal mucins. The effect of salicylate on glycoprotein biosynthesis by sheep colonic and human gastric mucosal tissues in vitro. Biochem J 1968; 106: 645-58.","journal-title":"Biochem J"},{"key":"ref_21","first-page":"270","article-title":"Human gallbladder mucin accelerates nucleation of cholesterol","volume-title":"artificial bile. Gastroenterology","volume":"87","author":"Levy, P.F.; Smith, B.F.; LaMont, J.T.","year":"1984","unstructured":"Levy PF, Smith BF, LaMont JT. Human gallbladder mucin accelerates nucleation of cholesterol in artificial bile. Gastroenterology 1984; 87: 270-5."},{"key":"ref_22","first-page":"1088","article-title":"Human gallbladder mucin binds biliary lipids and promotes cholesterol crystal nucleation in model bile. J7 Lipid","volume":"28","author":"Smith, B.F.","year":"1987","unstructured":"Smith BF. Human gallbladder mucin binds biliary lipids and promotes cholesterol crystal nucleation in model bile. J7 Lipid Res 1987; 28: 1088-97.","journal-title":"Res"},{"key":"ref_23","first-page":"648","article-title":"Effect of mucous glycoprotein on nucleation time","volume-title":"of human bile. Gastroenterology 1985; 89","author":"Gallinger, S.; Taylor, R.D.; Harvey, P.R.C.; Petrunka, C.N.; Strasberg, S.M.","unstructured":"Gallinger S, Taylor RD, Harvey PRC, Petrunka CN, Strasberg SM. Effect of mucous glycoprotein on nucleation time of human bile. Gastroenterology 1985; 89: 648-58."},{"key":"ref_24","first-page":"1319","article-title":"Mucous glycoprotein (MG) concentrations in normal and abnormal gallbladder (GB) bile and the effect of MG on nucleation time","volume":"86","author":"Gallinger, S.; Harvey, P.R.C.; Strasberg, S.M.","year":"1984","unstructured":"Gallinger S, Harvey PRC, Strasberg SM. Mucous glycoprotein (MG) concentrations in normal and abnormal gallbladder (GB) bile and the effect of MG on nucleation time. Gastroenterology 1984; 86: A1319.","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/hep.1840110402","article-title":"Isolation of a potent cholesterol nucleation promoting activity from human gallbladder bile. Role in the pathogenesis of gallstone disease","volume":"11","author":"Groen, A.K.; Noordam, C.; Drapers, J.A.G.; Egbers, P.; Jansen, P.L.M.; Tytgat, G.N.J.","year":"1990","unstructured":"Groen AK, Noordam C, Drapers JAG, Egbers P, Jansen PLM, Tytgat GNJ. Isolation of a potent cholesterol nucleation promoting activity from human gallbladder bile. Role in the pathogenesis of gallstone disease. Hepatology 1990; 11: 525-33.","journal-title":"Hepatology"},{"key":"ref_26","first-page":"318","article-title":"Con A-binding biliary protein contains a lipoprotein with nucleation promoting activity","volume":"100","author":"Groen, A.K.; de Brujin, M.A.C.; Goldhoorn, B.G.; van Marle, J.; Tytgat, G.N.J.","year":"1991","unstructured":"Groen AK, de Brujin MAC, Goldhoorn BG, van Marle J, Tytgat GNJ. Con A-binding biliary protein contains a lipoprotein with nucleation promoting activity. Gastroenterology 1991; 100: A318.","journal-title":"Gastroenterology"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.33.8.1109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T14:57:37Z","timestamp":1765637857000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.33.8.1109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,8]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[1992,8,1]]},"published-print":{"date-parts":[[1992,8]]}},"alternative-id":["10.1136\/gut.33.8.1109"],"URL":"https:\/\/doi.org\/10.1136\/gut.33.8.1109","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[1992,8]]}}}