Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine.

Cholecystokinin has previously been shown to produce a rise in immunoglobulin A (IgA) antibodies in the intestinal fluid of human volunteers. Whether the source of these antibodies was pancreatic, biliary, or mucosal had not been defined. The object of the present investigation was to study factors involved in regulating the release of IgA and IgG antibodies from the intestinal mucosa. Hooded-Lister rats were sensitized to ovalbumin. After the sensitization protocol, which lasted 21 days, the rats were anesthetized and a segment of intestine 10 cm long was isolated and perfused in vivo. This segment was flushed with normal saline for 30 min to remove all pancreatic, biliary, and other secretions. It was found in this model that after the intravenous injection of cholecystokinin-octapeptide there was a rise of IgA and IgG antibodies within 2.5 min. Significantly increased secretion of IgA lasted for 10 min, and increased secretion of IgG lasted for 20 min. The cholecystokinin antagonist proglumide reduced the secretions of both immunoglobulins. Atropine reduced baseline IgA secretion by one-half. Intragastric protein hydrolysate, which left the body through the severed end of the duodenum, also raised IgA and IgG levels significantly in the perfused intestine. Control animals receiving intragastric normal saline did not have an elevation of IgA or IgG levels. The phenomena described here demonstrate that the rate of IgA release from the mucosa is influenced by endocrine and nervous stimuli. The rate of IgG release is, as far as could be ascertained, only under endocrine control and not significantly influenced by the cholinergic antagonist atropine.