Fykse Vidar, Coy David H, Waldum Helge Lyder, Sandvik Arne Kristian
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway.
Br J Pharmacol. 2005 Feb;144(3):416-21. doi: 10.1038/sj.bjp.0706094.
Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst(1-5)), of which sst(2) is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst(2)-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 microM PRL-2903. With 10 microM 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 microM 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 microM PRL-2903 increased acid output from baseline 8.5+/-1.8 to 37.4+/-11 micromol h(-1); P=0.017. When combined with 10 microM 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.
生长抑素是胃酸分泌的强效抑制剂。其作用通过五种特定的受体亚型（sst(1 - 5)）介导，其中sst(2)在肠嗜铬样（ECL）细胞和壁细胞上占主导地位。为研究生长抑素的旁分泌机制，使用了sst(2)特异性拮抗剂PRL - 2903。在完全分离、血管灌注的大鼠胃中研究了PRL - 2903对胃酸分泌和组胺释放的影响。此外，还研究了蛙皮素单独及与PRL - 2903联合使用后组胺和胃泌素的释放情况。结果以平均值±平均标准误差（s.e.m.）表示。PRL - 2903浓度依赖性地使静脉组胺浓度从基础值55.6±7.5增加到50μM PRL - 2903时的367±114 nM。使用10μM PRL - 2903时，静脉组胺输出量从基线的6.2±0.5增加到20.9±4.9 nmol h(-1)；P = 0.008。520 pM胃泌素与10μM PRL - 2903联合使用使静脉组胺输出量从单独使用胃泌素时的41.7±7.3 nmol h(-1)增加到95.2±9.8 nmol h(-1)；P = 0.016。此外，10μM PRL - 2903使酸输出量从基线的8.5±1.8增加到37.4±11 μmol h(-1)；P = 0.017。当与10μM雷尼替丁联合使用时，PRL - 2903未显著刺激胃酸分泌。蛙皮素/PRL - 2903使静脉组胺浓度从50.4±14.8增加到292±64.2 nM；P = 0.008，胃泌素浓度从38.6±13.1增加到95.8±20.3 pM；P = 0.037。内源性生长抑素对胃黏膜组胺和胃泌素的释放持续发挥抑制作用，并显著降低基础胃酸分泌。
