Cholera Toxin-Induced Glycoprotein Secretion in Rabbit Small Intestine

Abstract

Few studies are available defining the mechanisms involved in the control of intestinal glycoprotein secretion, including the role of cyclic nucleotides. As suggested by the routine appearance of rice-water stools in Asiatic cholera, cholera toxin appears to have a stimulatory effect on intestinal glycoprotein secretion. In this study we report the effect of crude cholera toxin on in vivo rabbit intestinal glycoprotein secretion for up to 12 hr. Intraluminal toxin exposure markedly increased ileal mucosal cAMP content and net fluid secretion. Glycoprotein secretion as measured by hexosamine output in acid-precipitable, lipid-free material increased markedly in both ileal and jejunal loops when compared with control (heat-inactivated toxin). Peak output was observed at 4-5 hr, followed by a rapid decline to a new, but increased, steady-state rate of secretion. An identical glycoprotein secretion' pattern was observed when purified cholera enterotoxin was used. To investigate the relationship of ion transport to glycoprotein secretion, hypertonic mannitol (450 mOsm/kg) was used as an osmotic stimulus of fluid secretion. Fluid output was as rapid as noted after cholera toxin, but glycoprotein secretion was not significantly different from control, suggesting that intestinal glycoprotein secretion after cholera toxin is not simply a result of fluid movement. Intraarterial theophylline was infused at 10 μmol/min for 4 hr in order to further implicate increased mucosal cAMP content in the control of glycoprotein secretion. Both fluid and glycoprotein secretion were increased by theophylline, supporting the hypothesis that cholera toxin-stimulated glycoprotein output is mediated by cAMP. Lastly, the mucosal glycoprotein content of ileal mucosa was measured after cholera toxin exposure and noted to decrease by 40% after 8 hr. We conclude that cholera toxin is a potent stimulus for intestinal glycoprotein secretion. This increased output of glycoproteins appears to be controlled by increased levels of mucosal cAMP, rather than simply being a consequence of net fluid secretion. Based on the pattern of glycoprotein output, cholera toxin may stimulate intestinal glycoprotein biosynthesis in addition to stimulating intestinal secretion of glycoproteins.