Lloyd K C, Wang J, Aurang K, Grönhed P, Coy D H, Walsh J H
Research Services, Department of Veterans Affairs, West Los Angeles Medical Center, California.
Am J Physiol. 1995 Jan;268(1 Pt 1):G102-6. doi: 10.1152/ajpgi.1995.268.1.G102.
Somatostatin is a potent inhibitor of gastric acid secretion. Recently, at least five distinct somatostatin receptor subtypes (SSTR) have been characterized and evaluated using relatively selective peptide analogues of somatostatin. We sought to determine which somatostatin receptor subtypes are involved in peripheral regulation of gastric acid secretion. Fasted, male Sprague-Dawley rats were anesthetized and were implanted with a double-lumen cannula in the stomach. Acid secretion was measured in gastric samples collected every 10 min by backtitration to pH 7. After a 30-min basal period, a 2-h intravenous infusion of pentagastrin (24 micrograms.kg-1.h-1 i.v.) was started. During the second pentagastrin hour, a 1-h intravenous infusion of either vehicle (0.1% canine serum albumin in 0.9% saline) or somatostatin receptor agonists was begun. The somatostatin receptor agonists included peptides with relative specificity for SSTR1-5 (somatostatin-14; 10 nmol.kg-1.h-1); SSTR2, SSTR3, and SSTR5 [SMS-(201-995); 10 nmol.kg-1.h-1]; SSTR2 (1-1,000 nmol.kg-1.h-1); SSTR3 (10-1,000 nmol.kg-1.h-1); and SSTR5 (10-1,000 nmol.kg-1.h-1). The SSTR2 agonist decreased pentagastrin-stimulated acid secretion dose dependently, from 82 +/- 7% of maximum acid output at 1 nmol.kg-1.h-1 to 4 +/- 7% of maximum at 100 nmol.kg-1.h-1. At 10 nmol.kg-1.h-1, the SSTR2 agonist inhibited acid secretion (40 +/- 7% of maximum) similarly to somatostatin (37 +/- 4% of maximum) and SMS-(201-995) (31 +/- 4% of maximum). The SSTR2 agonist inhibited acid secretion approximately 10- to 100-fold more potently than either the SSTR3 or the SSTR5 agonist. These results indicate that somatostatin regulates gastric acid secretion by activation of SSTR2 receptors.
生长抑素是胃酸分泌的强效抑制剂。最近，至少已鉴定出五种不同的生长抑素受体亚型（SSTR），并使用生长抑素的相对选择性肽类似物进行了评估。我们试图确定哪些生长抑素受体亚型参与胃酸分泌的外周调节。将禁食的雄性Sprague-Dawley大鼠麻醉，并在胃内植入双腔插管。通过回滴定至pH 7，每10分钟收集一次胃样本，测量胃酸分泌。在30分钟的基础期后，开始静脉输注五肽胃泌素（24微克·千克⁻¹·小时⁻¹，静脉注射）2小时。在五肽胃泌素输注的第二个小时内，开始静脉输注载体（0.9%盐水中的0.1%犬血清白蛋白）或生长抑素受体激动剂1小时。生长抑素受体激动剂包括对SSTR1-5具有相对特异性的肽（生长抑素-14；10纳摩尔·千克⁻¹·小时⁻¹）；SSTR2、SSTR3和SSTR5 [SMS-(201-995)；10纳摩尔·千克⁻¹·小时⁻¹]；SSTR2（1-1000纳摩尔·千克⁻¹·小时⁻¹）；SSTR3（10-1000纳摩尔·千克⁻¹·小时⁻¹）；以及SSTR5（10-1000纳摩尔·千克⁻¹·小时⁻¹）。SSTR2激动剂以剂量依赖性方式降低五肽胃泌素刺激的胃酸分泌，从1纳摩尔·千克⁻¹·小时⁻¹时最大胃酸分泌量的82±7%降至100纳摩尔·千克⁻¹·小时⁻¹时最大胃酸分泌量的4±7%。在10纳摩尔·千克⁻¹·小时⁻¹时，SSTR2激动剂抑制胃酸分泌（最大胃酸分泌量的40±7%），与生长抑素（最大胃酸分泌量的37±4%）和SMS-(201-995)（最大胃酸分泌量的31±4%）相似。SSTR2激动剂抑制胃酸分泌的效力比SSTR3或SSTR5激动剂大约强10至100倍。这些结果表明，生长抑素通过激活SSTR2受体来调节胃酸分泌。
