Schally A V, Colaluca J, Paulson D, Carter W H, Neitzschman H R, Lafaye H, Cai R Z
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, LA.
Int J Pept Protein Res. 1990 Sep;36(3):267-74. doi: 10.1111/j.1399-3011.1990.tb00977.x.
The effects of several superactive analogs of somatostatin on gastric acid response to various exogenous and endogenous stimulants were investigated in conscious dogs and rats with gastric fistulae (GF). The inhibition was compared to that induced by somatostatin-14 (S-S-14) at two dose levels. Several octapeptide analogs of somatostatin including D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), which were superactive in tests on suppression of GH levels, were 4-5 times more potent than S-S-14 in inhibiting desglugastrin-stimulated gastric acid secretion in GF dogs. The analog RC-160 also reduced the rise in serum gastrin levels and gastric acid secretion induced by sham feeding (SF) in dogs with gastric and esophageal fistulae (EF), but did not decrease food consumption. Gastric acid secretion induced by histamine (80 micrograms/kg/h) in dogs was not affected by 1-5 micrograms/kg/h of analog RC-121 or by 5 micrograms/kg/h of S-S-14. Analogs RC-160, RC-121, and RC-98-I (D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2) and others also powerfully inhibited desglugastrin-induced potent as S-S-14 in dogs but its activity was higher in rats. The results indicate that octapeptide analogs which are superactive in GH-inhibition tests are also more potent than S-S-14 in suppressing gastric acid secretion. These findings may be of clinical value.
在有意识的患有胃瘘（GF）的犬和大鼠中，研究了几种生长抑素的超活性类似物对胃酸对外源性和内源性刺激物反应的影响。将这种抑制作用与两种剂量水平的生长抑素-14（S-S-14）所诱导的抑制作用进行比较。几种生长抑素的八肽类似物，包括D-苯丙氨酸-半胱氨酸-酪氨酸-D-色氨酸-赖氨酸-缬氨酸-半胱氨酸-色氨酸- NH₂（RC-160）和D-苯丙氨酸-半胱氨酸-酪氨酸-D-色氨酸-赖氨酸-缬氨酸-半胱氨酸-苏氨酸- NH₂（RC-121），它们在抑制生长激素水平的试验中具有超活性，在抑制GF犬中去甘氨酰胃泌素刺激的胃酸分泌方面，其效力比S-S-14强4至5倍。类似物RC-160还降低了患有胃和食管瘘（EF）的犬假饲（SF）所诱导的血清胃泌素水平升高和胃酸分泌，但并未减少食物摄入量。犬中组胺（80微克/千克/小时）诱导的胃酸分泌不受1至5微克/千克/小时的类似物RC-121或5微克/千克/小时的S-S-14的影响。类似物RC-160、RC-121和RC-98-I（D-色氨酸-半胱氨酸-苯丙氨酸-D-色氨酸-赖氨酸-苏氨酸-半胱氨酸-苏氨酸- NH₂）等在犬中也能强力抑制去甘氨酰胃泌素诱导的胃酸分泌，其效力与S-S-14相当，但在大鼠中的活性更高。结果表明，在生长激素抑制试验中具有超活性的八肽类似物在抑制胃酸分泌方面也比S-S-14更有效。这些发现可能具有临床价值。
