Secretin and cholecystokin / pancreozymin in combination in the inhibition of gastric acid secretion

Inhibition of gastric acid secretion is caused when the mucosa of the upper small intestine is bathed either by fat (Feng, Hou, and Lim, 1929), acid (Sokolov, 1904) or hyperosmolar solutions (Konturek and Grossman, 1965). The studies of Andersson (1960) suggest that the inhibition caused by acid in the duodenum is mediated by a humoral agent. There is therefore interest in the possible inhibitor properties on gastric acid secretion of extracts prepared from duodenal mucosa (Jorpes, 1968). Under certain experimental conditions in dogs, relatively pure secretin (Gillespie and Grossman, 1964a; Wormsley and Grossman, 1964) and relatively pure cholecystokinin/pancreozymin (Gillespie and Grossman, 1964, Bedi, Govaerts, Master, and Gillespie, 1967) have been demonstrated to inhibit Heidenhain pouch acid responses to stimulation by gastrin and it has been suggested that these agents may in fact be the principal mediators of the inhibition. There is evidence of potentiation at the level of the acid-producing cells between pairs of stimulants, eg, gastrin extract and stable choline ester (Gillespie and Grossman, 1964b), and gastrin and histamine (Passaro, Gillespie, and Grossman, 1964). Bedi, Debas, Gillespie, and Gillespie (1971) have also shown potentiation between bile salts and acetylcholine in the release of gastrin from the pyloric antrum. It is possible that potentiation may also exist between various inhibitors of gastric acid secretion. The present experiments were therefore designed to explore the possibility that both secretin and cholecystokinin/pancreozymin acting together may result in facilitated or potentiated inhibition.