Nonparallel secretion of pepsinogen and acid by gastric oxyntopeptic cells of the toad (Bufo marinus)

Pepsinogen and HCl secretion in the amphibian stomach are performed by a single cell type, the oxyntopeptic cell. These functions were studied in gastric mucosae of toads (Bufo marinus) mounted in Ussing-type chambers. HCl and peptic activity of luminal fluid were measured by titration and proteolysis of albumin, respectively. Distribution of pepsinogen in the gastric mucosa was heterogeneous, activity being highest in the proximal part of the stomach. Zymogen granules in the oxyntopeptic cell were more abundant in the deeper cells of the glands and in the fundus. On stimulation, the granules were released into the lumen of the glands by exocytosis. Histamine, forskolin, or carbachol alone each induced an increase in HCl and pepsinogen secretion. Carbachol after maximal histamine or forskolin stimulation produced an extra increase in both secretions that was greater for pepsinogen response. Similarly, joint addition of carbachol and histamine was more potent than histamine alone for both parameters; however, the effect was greater on pepsinogen release. Pretreatment with cimetidine blocked HCl and pepsinogen responses to carbachol but did not affect responses to forskolin. Addition of omeprazole to forskolin-stimulated mucosae uncoupled the two secretions, inducing a total inhibition of HCl secretion with a slight reduction in pepsinogen secretion. Thus pepsinogen release, similar to HCl secretion, is sensitive to cAMP and Ca(2+)-dependent secretagogues. However, the action of Ca2+ would require the previous elevation of cAMP induced by the different secretagogues. In such a case, the increase in intracellular Ca2+ would result in a nonparallel activation of the two secretions.