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Since the ingestion of fat results in the inhibition of the secretion of autotransplanted (i. e., completely denervated) gastric pouches (Feng, Hou and Lim), the mechanism concerned must be a humoral one. It was thought that as fat causes the ejection of bile into the duodenum, the reabsorbed bile (salts) might be the humoral agent, but this has been proved not to be the case (Kosaka and Lim). The influence of fat on the gall bladder has been shown by Ivy and Oldberg to be due also to a humoral agent. Having a sample of Ivy's gall bladder hormone, viz., cystokinin, on hand, this was tried and found to inhibit gastric secretion in large doses (5 gm. per kg.). An attempt was therefore made to recover the gastric inhibitory agent from the intestine. The upper small intestine of dogs (under ether or decerebrate) was ligatured in segments about 10 cm. long, and 50 cc. of olive oil introduced into alternate segments. After one hour, the intestine was removed and the mucosa exposed and unexposed to oil separately scraped off and extracted with N/10 HCl at a relatively low temperature (about 60°C.). Extracts have also been made simply with saline. Extracts from mucosa exposed to oil inhibit gastric secretion to a meat meal, when injected either intravenously or subcutaneously into Heidenhain-pouch dogs, the degree of inhibition produceable being comparable with that caused by the oral ingestion of fat (see Table I). Similar doses of the saline extract appear to have no effect on either the pancreatic or biliary secretion and do not depress the blood pressure. Further, when these extracts are heated to 80-100°C. for 10 minutes, the inhibitory effect is removed, and if HCl is added before heating, a gastric stimulating action is frequently obtained.
Kosaka et al. (Sun,) studied this question.