Stimulation of oxyntic and histaminergic cells in gastric mucosa by gastrin C-terminal tetrapeptide.

Gastrin tetrapeptide (TG) stimulation of H+ secretion and histamine release and their relationship were characterized in isolated amphibian gastric mucosa. TG released histamine and stimulated H+ secretion. Dose-response curves to TG showed nonparallel increases in both parameters. In tachyphylaxis experiments, there was no correlation between histamine release and H+ secretion. Comparison of cimetidine inhibitory dose-response curves of maximal TG or histamine stimulation showed a much higher sensitivity for TG-stimulated H+ secretion. This suggests that the pericellular histamine concentration released by TG was lower than that needed for maximal response. In mucosae maximally stimulated by histamine, TG induced a further increase in H+ secretion. In the presence of cimetidine, there was potentiation between TG and dibutyryl cAMP that was dependent on the presence of extracellular calcium. The results are interpreted to indicate that TG (or gastrin) stimulates H+ secretion through different mechanisms: 1) direct stimulation of the oxyntic cell dependent on extracellular calcium, 2) potentiation between gastrin and histamine, and 3) release of histamine from paracrine cells. Direct stimulation of the oxyntic cell by TG is not sufficient to trigger H+ secretion. Potentiation between TG and histamine at the oxyntic cell may result from interaction between TG-induced increases in intracellular Ca2+ and histamine-induced increases in intracellular cAMP.