Acute and chronic models for hypersecretion of intestinal mucin.
Mucin secretion was examined in three functional models relevant to human disease, using rat small intestinal rings or in situ loops, [3H]glucosamine precursor labelling, gel chromatography and a specific radioimmunoassay for mucin. As a model for acute bacterial secretory diarrhoea, tissues were exposed to cholera toxin for up to 4 h. Both stored and newly synthesized radioactive glycoproteins were secreted in amounts twofold to threefold above control levels. Immunoreactive mucin secretion increased fivefold to eightfold. Other agents known to raise cAMP levels did not stimulate mucin secretion, suggesting that cholera may release mucin by a non-cAMP-dependent mechanism. Sepharose 2B chromatography indicated that secreted mucin was smaller in size than intracellular mucin and had compositional differences suggestive of 'immaturity' or protein contamination. In chronically (seven days) reserpinized rats, used as a model of glycoprotein abnormalities relevant to cystic fibrosis, mucin secretion increased twofold to threefold, but the most prominent abnormality was a marked increase in [3H]glucosamine incorporation into all tissue glycoproteins. On purification, the intracellular mucin of reserpine-treated rats had the same composition as mucin from control rats, but the former was smaller in size and had a higher specific radioactivity. Mucin hypersecretion in reserpinized rats may therefore be secondary to a primary and chronic hyperstimulation of mucin biosynthesis. A model of intestinal 'anaphylaxis' or immune-mediated diarrhoea was created in Hooded Lister rats by immunizing with egg albumin (10 micrograms) and challenging with the same antigen in intestinal loops 14 days later. After 4 h, total protein, DNA and brush border sucrase were increased in the lumen. Enhancement of mucin secretion did not occur, however, and therefore does not seem to be a particular feature of the pathophysiology of this model.
D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D002772:Cholera Toxin; D003550:Cystic Fibrosis / Q000139:chemically induced / Q000503:physiopathology*; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D051381:Rats; D012110:Reserpine
D006023:Glycoproteins; D009077:Mucins; D012110:Reserpine; D002772:Cholera Toxin