Paracrine regulation of gastric acid secretion by fundic somatostatin

The isolated, luminally perfused mouse stomach was used to determine whether somatostatin cells located in proximity to parietal cells exert a paracrine influence on acid secretion. Acid secretion in response to histamine and pentagastrin was accompanied by a dose-dependent increase in somatostatin secretion. Incubation of the stomach with somatostatin antiserum (final dilution 1:100), but not with normal serum, augmented significantly basal and secretagogue-stimulated acid secretion. The augmentation was most evident with submaximal stimuli (92 +/- 18%, P less than 0.01, with 15 microM pentagastrin and 160 +/- 6%, P less than 0.001, with 5 microM histamine) and least evident with maximal stimuli (30 +/- 12%, P less than 0.05, with 200 microM histamine). The acid response to submaximal field stimulation (10 V, 20 Hz, 0.5 ms), which was accompanied by an increase in somatostatin secretion, was also augmented by somatostatin antiserum (115 +/- 12%, P less than 0.01), whereas the response to maximal field stimulation (20 V, 20 Hz, 0.5 ms), which was accompanied by a decrease in somatostatin secretion, a typically cholinergic effect, was not augmented further. It is concluded that fundic somatostatin modulates the acid secretory response to paracrine (histamine), hormonal (gastrin), and neural (acetylcholine) stimuli and that cholinergic stimulation of acid secretion reflects both the direct effect of acetylcholine on the parietal cell and its ability to eliminate the paracrine restraint exerted by somatostatin.