Somatostatin-receptor 2 (sst2)-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach

摘要

Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst1–5), of which sst2 is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst2-specific antagonist PRL-2903 was used.Effects of PRL-2903 on acid secretion and release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the release of histamine and gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.).PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h−1; P=0.008. The combination of 520 pM gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h−1 with gastrin alone to 95.2±9.8 nmol h−1; P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h−1; P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037.Endogenous somatostatin exerts a continuous restraint on histamine and gastrin release from the gastric mucosa and significantly reduces baseline acid secretion.