Actions of a gastrin agonist isolated from antral mucosa: histamine-like effects; comparison with histamine
Vatier, J.; De Mestier, P.; Bourgeois, M.; Poitevin, C.; Terhederbrugge, R.; Robert, J.C.; Vitré, M.T.; Bonfils, S.
Journal de Physiologie 77(6-7): 683-693
ISSN/ISBN: 0021-7948 PMID: 6793719 Accession: 004661582
It was previously demonstrated that an extract of antrum gastric mucosa (substance S), which potentiates gastrin (G) acid secretion, has an additive effect in histamine (H). Some biological properties of S were different from those of H. Thus, S evoked a pepsin secretion to a greater degree than H and the ileal contractions induced were not inhibited by mepyramine. A new step in the chromatographic procedure produced a highly purified extract. The purpose was 2-fold: in dogs with innervated stomach and denervated Heidenhain pouches, to compare the action of S with H on the gastric secretion and to estimate the degree of the purification in comparison with the first extract S. The purified extract was comparable to the first; but it was 10 times more potent. S alone was able to stimulate the secretions of gastric acid and pepsin and to potentiate the G-stimulated secretion of acid. H also potentiates the G-stimulated secretions of acid. There were some analogies between S and H on the gastrinic stimulations. In acid secretion, the associations G + H and G + S shifted the dose response curve to the left. In all cases, the maximal response was the same. In pepsin secretion there was no potentiation, and the ratio pepsin output/acid output decreased. The stimulation was more potent on the parietal cell mass than the chief cell mass. With G + H, the pepsin output increased, while with G + S the pepsin output decreased; however, H and S have some different characteristics. In acid secretion, to compare S and H, it was possible to transform S into its H equivalent using dose response curves. This translation was possible on the main stomach and the denervated pouch. If S was similar to H, the same results should be obtained especially for G + S 10 g/h and G + H 60 .mu.g/h. The maximal responses were similar. On the main stomach, the gastric acid secretion was not significantly different for G + S or for G + H. On the denervated pouch the combination of G + S appeared more potent than the combination G + H; the maximal response remained the same. This suggests that S alters the sensitivity of the parietal cell to G to a greater degree than H. In pepsin secretion, S alone is twice as potent on pepsin secretion than G and H alone. The transformation of S into its H equivalent was not possible. There were no significant differences in the pepsin output for G + S and G + H. Therefore, H and S were able to increase the G-stimulated secretion of acid. The curves of outputs of fixed acid secreted by the main stomach in relation to the dosages of G and H or S are shown. On the denervated pouch, 2 different curves were obtained for the same acid outputs by substitution of S in its H equivalent. Although H is known to be a stimulant of gastric acid secretion, its synthesis, localization and activity remain unknown. The compound described here, which potentiates G and has H-like activity, could, in fact, be H in a native or physiological state.