Somatostatin receptor subtype 2 mediates inhibition of gastrin and histamine secretion from human, dog, and rat antrum.

BACKGROUND & AIMS: In gastric antrum, somatostatin exerts a tonic inhibitory influence on gastrin and histamine secretion. Five different subtypes of somatostatin receptors, designated sst1-5, have been identified. sst2, sst3, and sst5 subtypes have been localized to the stomach by molecular biological techniques. The aim of this study was to identify the sst subtype regulating gastrin and histamine secretion in human, dog, and rat stomach.

METHODS

Mucosal segments from human, dog, and rat antrum were superfused with various concentrations of somatostatin 14 and somatostatin analogues selective for sst2, sst3, and sst5. Gastrin and histamine were measured by radioimmunoassay.

RESULTS

Somatostatin 14 and the sst2 agonist EC 5-20 inhibited gastrin and histamine secretion from all three species in a concentration-dependent manner, whereas the sst3 and sst5 agonists had no significant effect. Neutralization of endogenous somatostatin with the somatostatin antibody increased gastrin and histamine secretion. The increases were not affected by the gastrin antagonist but were abolished by the sst2 agonist, implying that the inhibitory influence of ambient somatostatin is exerted directly on the histamine cell rather than indirectly via changes in gastrin secretion.

CONCLUSIONS

Somatostatin inhibits gastrin and histamine secretion in human, dog, and rat antrum by activating sst2 receptors on gastrin and histamine cells.