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.
The mechanism of action of bombesin, also known as gastrin-releasing peptide (GRP), on somatostatin secretion was examined separately in superfused segments of rat antral and fundic mucosa. Bombesin/GRP (1 nM) stimulated somatostatin secretion from both regions. In fundic segments, the somatostatin response was strongly inhibited (86%; P less than 0.01) by tetrodotoxin (5 microM) but augmented by atropine (1 microM) (P less than 0.01). In antral segments, both tetrodotoxin and atropine augmented the somatostatin response to bombesin/GRP by 42-45% (P less than 0.01), whereas the gastrin antagonist L 365260 (1 microM) abolished it. The gastrin antagonist augmented the gastrin response to bombesin/GRP by 103% (P less than 0.01). The results indicate that bombesin/GRP stimulates somatostatin secretion by distinct mechanisms in the fundus and antrum. In the fundus, bombesin/GRP acts indirectly on somatostatin cells by activating stimulatory noncholinergic neurons and, to a lesser extent, inhibitory cholinergic neurons. In the antrum, bombesin/GRP acts indirectly on somatostatin cells by stimulating release of gastrin and, to a lesser extent, by activating inhibitory cholinergic neurons. A dual paracrine pathway links gastrin and somatostatin secretion in the antrum.
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