Cholera toxin stimulates secretion of immunoreactive intestinal mucin

In vitro secretion of goblet cell mucin from rat small intestine was measured using a double-antibody radioimmunoassay for mucin. Cholera toxin (12.5-50 mg crude filtrate/ml) added to incubations of intestinal slices caused a dose-dependent increase in mucin secretion. By 90 min there was a four- to fivefold enhancement in secretion over noncholera-treated controls. Crude filtrate (dialyzed or nondialyzed) was a more effective mucin secretogogue than purified enterotoxin. Secretion was also assessed by administering [1-14C]glucosamine intraperitoneally to rats in vivo and 3 h later monitoring in vitro secretion of radioactive glycoprotein from intestinal slices. Cholera filtrate (12.5-50 mg/ml) caused a 1.5- to 2.0-fold enhancement in secretion after 90 min. The radioactivity data, however, underestimated total mucin secretion and the dependency of secretion on the dose of cholera filtrate. Cholera preparations also caused an enhancement (20-30% over controls) in the incorporation of [3H]glucosamine into tissue acid-precipitable glycoprotein, indicating a stimulation of glycoprotein synthesis. In the same experiments it was noted that the secretion of 3H-labeled (i.e., newly glycosylated) glycoprotein was increased 2.5- to 3.0-fold over untreated controls. Assuming that radioactivity partially reflects mucin synthetic and secretory events, it is possible, therefore, that cholera toxin promotes the release of both "old" mucin from storage granules as well as the synthesis and secretion of "new" mucin formed in goblet cells during incubation.