Fung L C, Greenberg G R
Department of Medicine, University of Toronto, Ontario, Canada.
Regul Pept. 1997 Feb 26;68(3):197-203. doi: 10.1016/s0167-0115(96)02122-2.
Five somatostatin receptor subtypes (SSTR) have been cloned and characterized in various tissues, including the gastrointestinal tract. This study examined which receptor subtypes mediate the inhibitory actions of somatostatin on gastric acid secretion and gastrin release in conscious dogs. Peptide agonists with relatively high specificity for SSTR1-5 (somatostatin-14), SSTR2 (MK-678), SSTR3 (L-362823), and SSTR5 (L-362855) were infused i.v. after nutrient-stimulated gastric acid secretion and gastrin release with intraduodenal perfusions of 8% peptone and after secretagogue-stimulated acid secretion with gastrin (75 pmol kg-1 h-1) or histamine (20 micrograms kg-1 h-1). At 1000 pmol kg-1 h-1, the SSTR2 agonist inhibited peptone-stimulated acid output to baseline (P < 0.001), whereas the SSTR3 agonist decreased acid output by 58 +/- 6% (P < 0.01): the SSTR5 agonist was without effect. The SSTR2 agonist at 100 pmol kg-1 h-1 also abolished the rise of plasma gastrin. At 50 pmol kg-1 h-1 i.v. infusions of S-14, to simulate circulating S-14 rises after nutrients, decreased peptone-stimulated acid secretion by 58 +/- 8% (P < 0.01), whereas the SSTR2 agonist inhibited gastric acid by 96 +/- 2% (P < 0.001); the SSTR3 agonist was without effect. S-14 or the agonists at 50 pmol kg-1 h-1 did not alter elevations of plasma gastrin. S-14 and the SSTR2 agonist at 50 pmol kg-1 h-1 decreased gastrin-stimulated acid secretion by 42 +/- 8% (P < 0.01) and 78 +/- 4% (P < 0.001), respectively but the SSTR3 and SSTR5 agonists were without effect. In contrast, histamine-stimulated acid secretion was not altered by 1000 pmol kg-1 h-1 S-14 or the agonists. These results in conscious dogs suggest that the inhibitory actions of circulating S-14 on nutrient and gastrin-stimulated acid secretion include activation of the SSTR-2 subtype. Regulation of gastrin release by S-14 may also occur via SSTR-2, but not through an endocrine mechanism. Factors in addition to gastrin and histamine modulate intestinal protein-stimulated acid secretion yet include peripheral S-14 inhibition via SSTR2 activation.
已经在包括胃肠道在内的各种组织中克隆并鉴定出五种生长抑素受体亚型（SSTR）。本研究检测了哪些受体亚型介导生长抑素对清醒犬胃酸分泌和胃泌素释放的抑制作用。对SSTR1 - 5（生长抑素 - 14）、SSTR2（MK - 678）、SSTR3（L - 362823）和SSTR5（L - 362855）具有相对高特异性的肽激动剂在十二指肠内灌注8%蛋白胨刺激胃酸分泌和胃泌素释放后，以及用胃泌素（75 pmol kg-1 h-1）或组胺（20 μg kg-1 h-1）刺激胃酸分泌后静脉注射。在1000 pmol kg-1 h-1时，SSTR2激动剂将蛋白胨刺激的酸分泌抑制至基线水平（P < 0.001），而SSTR3激动剂使酸分泌减少58±6%（P < 0.01）：SSTR5激动剂无作用。100 pmol kg-1 h-1的SSTR2激动剂也消除了血浆胃泌素的升高。静脉注射50 pmol kg-1 h-1的S - 14以模拟营养物质后循环中S - 14的升高，使蛋白胨刺激的胃酸分泌减少58±8%（P < 0.01），而SSTR2激动剂抑制胃酸96±2%（P < 0.001）；SSTR3激动剂无作用。50 pmol kg-1 h-1的S - 14或激动剂未改变血浆胃泌素的升高。50 pmol kg-1 h-1的S - 14和SSTR2激动剂分别使胃泌素刺激的胃酸分泌减少42±8%（P < 0.01）和78±4%（P < 0.001），但SSTR3和SSTR5激动剂无作用。相比之下，1000 pmol kg-1 h-1的S - 14或激动剂未改变组胺刺激的胃酸分泌。清醒犬的这些结果表明，循环中S - 14对营养物质和胃泌素刺激的胃酸分泌的抑制作用包括SSTR - 2亚型的激活。S - 14对胃泌素释放的调节也可能通过SSTR - 2发生，但不是通过内分泌机制。除胃泌素和组胺外的因素调节肠道蛋白质刺激的胃酸分泌，但包括通过SSTR2激活的外周S - 14抑制。
