Section 5
Chapter 4,662

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

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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.

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