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 inhi bitory influence on gastrin and histamine secretion, Five different su btypes of somatostatin receptors, designated sst(1-5), have been ident ified. sst(2), sst(3), and sst(5) 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 so matostatin 14 and somatostatin analogues selective for sst(2), sst(3), and sst(5), Gastrin and histamine were measured by radioimmunoassay. Results: Somatostatin 14 and the sst(2), agonist EC 5-20 inhibited gas trin and histamine secretion from all three species in a concentration -dependent manner, whereas the sst(3), and sst(3), agonists had no sig nificant effect, Neutralization of endogenous somatostatin with the so matostatin antibody increased gastrin and histamine secretion, The inc reases were not affected by the gastrin antagonist but were abolished by the sst(2), agonist, implying that the inhibitory influence of ambi ent somatostatin is exerted directly on the histamine cell rather than indirectly via changes in gastrin secretion, Conclusions: Somatostati n inhibits gastrin and histamine secretion in human, dog, and rat antr um by activating sst(2), receptors on gastrin and histamine cells.