Inhibitory effect of secretin and cholecystokinin on Heidenhain pouch responses to gastrin extract and histamine

Abstract

MATERIALS AND METHODSFive dogs with Heidenhain type denervated fundic pouches created more than six months previously were studied.Secretin and cholecystokinin, prepared by the method of Jorpes and Mutt (1959), were obtained from Vitrum (Stockholm). Gastrin extract was prepared from hog antral mucosa by a modification of the method of Gregory and Tracy (1961) previously described (Gillespie and Grossman, 1963); doses are expressed as the equivalent weight in grams of wet antral mucosa.The dogs were deprived of food overnight before each test. The inhibitory action of the secretin and cholecystokinin was tested against a background of secretion stimulated by continuous intravenous infusion of gastrin extract or histamine given throughout each experiment by a Sigmamotor pump, the rate of flow being 20 ml. per hour. The concentration of gastrin extract or of histamine dihydrochloride in 0.9% sodium chloride solution was adjusted to give the desired dose rates. After the response had reached a plateau of at least four approximately equal successive 15-minute collections, a single intravenous injection of secretin or cholecystokinin (75 clinical units = 0.1 mg. for secretin, 3 mg. for cholecystokinin) was given and collections were continued at 15-minute intervals for at least one and a half hours.The acid concentration was determined by titration with 0.2N sodium hydroxide with phenol red indicator. The results are given as microequivalents per 15 minutes. The control output is the mean of the four 15-minute outputs immediately preceding the secretin or cholecystokinin injection, each subsequent 15-minute output being expressed as a percentage of the control response. In all instances duplicate observations were made on each dog. RESULTS

Effect of Secretin and Cholecystokinin on the Response of the Gastric Fistula Rat to Pentagastrin

“…Secretin has been shown to inhibit acid secretion stimulated by food and antral irrigation ( l ) , duodenal distension ( 2 ) , intestinal stimulation (3), and exogenous gastrin (4). Although pure secretin is a potent inhibitor of gastrin-stimulated secretion in the dog ( 5 ) , it has little effect on gastric acid secretion in the cat (6).…”

Effects of Metiamide and Propranolol on Gastric Secretion in Anesthetized Dogs

“…At present we have no explanation for these species differences. In addition to the data obtained with metiamide and propranolol, it is well known that both secretin and glucagon markedly inhibit the gastric secretion induced by gastrin but not that induced by histamine (14)(15)(16). We have already reported that atropine sulfate markedly inhibited the methacholine or tetragastrin stimulated gastric secretion but exerted less influence on histamine stimulated secretion in anesthetized dogs (17).…”

Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin‐related peptides in rabbit gastric glands.

“…Considering that cholecystokinin peptides inhibit parietal cell activity in vivo (Gillespie & Grossman, 1964;Brooks, Agosti, Bertaccini & Grossman, 1970;Sj6din, 1972;Holstein, 1982) and in vitro (Schepp, Ruoff & Maslinski, 1983;Bengtsson & Nilsson, 1989) (Davison & Najafi-Farashah, 1987), showing that the CCK antagonist dibutyryl cyclic GMP interferes with vagal inhibitory impulses possibly mediated by a CCK peptide.…”