Lloyd K C, Amirmoazzami S, Friedik F, Chew P, Walsh J H
Research Service, West Los Angeles Veterans Affairs Medical Center, California, USA.
Am J Physiol. 1997 Jun;272(6 Pt 1):G1481-8. doi: 10.1152/ajpgi.1997.272.6.G1481.
Somatostatin is a potent inhibitor of gastrin-stimulated acid secretion by activation of somatostatin receptor type 2 (sst2) in vivo, probably in part by blocking gastrin-stimulated histamine release from enterochromaffin-like cells expressing sst2. We propose that activation of sst2 may also regulate meal-stimulated acid secretion by blocking gastrin release from antral G cells. Using peptide analogs relatively selective for sst2 (NC-8-12), sst3 (BIM-23058), and sst5 (BIM-23052), we tested this hypothesis in two ways: first, in vivo by measuring plasma gastrin release during meal-stimulated acid secretion in dogs, and second, in vitro by measuring bombesin-stimulated gastrin release from an enriched culture of canine antral G cells. In vivo, a low dose (0.05 nmol.kg-1.h-1) of NC-8-12 inhibited acid secretion 56 +/- 16% without blocking gastrin release. A higher dose (1 nmol.kg-1.h-1) of NC-8-12 abolished acid secretion and inhibited gastrin release by 61 +/- 4%, whereas the highest dose (5 nmol.kg-1.h-1) inhibited gastrin release by 84 +/- 3%. Only the highest doses (5 nmol.kg-1.h-1) of BIM-23058 and BIM-23052 significantly inhibited gastrin release and acid secretion. In vitro, NC-8-12 (10(-9) M) reduced bombesin-stimulated gastrin release from antral G cells by 49 +/- 5%, whereas BIM-23058 and BIM-23052 were at least 100-fold less effective. These results indicate that somatostatin activation of sst2, but not sst3 or sst5, is the major pathway for somatostatin-induced inhibition of meal-stimulated gastrin release and acid secretion.
生长抑素是胃泌素刺激胃酸分泌的强效抑制剂，其在体内通过激活2型生长抑素受体（sst2）发挥作用，可能部分是通过阻断胃泌素刺激的组胺从表达sst2的肠嗜铬样细胞释放。我们提出，sst2的激活也可能通过阻断胃窦G细胞释放胃泌素来调节进餐刺激的胃酸分泌。使用对sst2（NC-8-12）、sst3（BIM-23058）和sst5（BIM-23052）具有相对选择性的肽类似物，我们通过两种方式验证了这一假设：第一，在体内，通过测量犬类进餐刺激胃酸分泌期间的血浆胃泌素释放；第二，在体外，通过测量蛙皮素刺激犬胃窦G细胞富集培养物中胃泌素的释放。在体内，低剂量（0.05 nmol·kg-1·h-1）的NC-8-12抑制胃酸分泌56±16%，而不阻断胃泌素释放。较高剂量（1 nmol·kg-1·h-1）的NC-8-12消除了胃酸分泌，并抑制胃泌素释放61±4%，而最高剂量（5 nmol·kg-1·h-1）抑制胃泌素释放84±3%。只有最高剂量（5 nmol·kg-1·h-1）的BIM-23058和BIM-23052显著抑制胃泌素释放和胃酸分泌。在体外，NC-8-12（10-9 M）使蛙皮素刺激的胃窦G细胞胃泌素释放减少49±5%，而BIM-23058和BIM-23052的效力至少低100倍。这些结果表明，生长抑素激活sst2而非sst3或sst5是生长抑素诱导抑制进餐刺激的胃泌素释放和胃酸分泌的主要途径。
