Hirst B H, Arilla E, Coy D H, Shaw B
Peptides. 1984 Sep-Oct;5(5):857-60. doi: 10.1016/0196-9781(84)90106-2.
The gastric inhibitory activity of cyclic hexa- and pentapeptide analogues of somatostatin was investigated in conscious cats with gastric fistulae. Gastric acid and pepsin secretions were stimulated by pentagastrin. Cyclo(Phe-Phe-D-Trp-Lys-Thr-Phe) showed no inhibition of acid secretion at molar doses up to 50-times the ID50 for somatostatin. This peptide inhibited pepsin secretion at the highest dose (50 micrograms kg-1 hr-1), and its potency is approximately 0.005 compared with somatostatin (1.0). Cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) inhibited acid (approximately 50%) and pepsin (approximately 85%) secretions, but the inhibition was not dose-related being similar with doses of 10 to 50 micrograms kg-1 hr-1. The cyclic pentapeptide, cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr), was inactive in the dose range studied, with a potency less than 0.01. Cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)] has been described as a somatostatin antagonist with respect to inhibition of growth hormone, insulin and glucagon release in rats [2]. Up to 60-fold molar excesses of this peptide failed to antagonise the inhibitory activity of somatostatin in the stomach. The results demonstrate that residues outside the central 6-11 region of somatostatin are very important for its gastric activity. The lack of gastric antagonistic activity of the pentapeptide antagonist indicates that these residues are likely to be involved in receptor recognition/binding.
在有意识的胃瘘猫中研究了生长抑素的环状六肽和五肽类似物的胃抑制活性。用五肽胃泌素刺激胃酸和胃蛋白酶分泌。环（苯丙氨酸-苯丙氨酸-D-色氨酸-赖氨酸-苏氨酸-苯丙氨酸）在高达生长抑素ID50的50倍摩尔剂量下未显示出对胃酸分泌的抑制作用。该肽在最高剂量（50微克/千克·小时-1）时抑制胃蛋白酶分泌，与生长抑素（1.0）相比其效力约为0.005。环（脯氨酸-苯丙氨酸-D-色氨酸-赖氨酸-苏氨酸-苯丙氨酸）抑制胃酸（约50%）和胃蛋白酶（约85%）分泌，但这种抑制与剂量无关，在10至50微克/千克·小时-1的剂量下相似。环状五肽环（7-氨基庚酰基-苯丙氨酸-D-色氨酸-赖氨酸-苏氨酸）在所研究的剂量范围内无活性，效力小于0.01。环[7-氨基庚酰基-苯丙氨酸-D-色氨酸-赖氨酸-苏氨酸（苄酯）]在大鼠中已被描述为一种关于抑制生长激素、胰岛素和胰高血糖素释放的生长抑素拮抗剂[2]。高达60倍摩尔过量的该肽未能拮抗生长抑素在胃中的抑制活性。结果表明，生长抑素中心6-11区域以外的残基对其胃活性非常重要。五肽拮抗剂缺乏胃拮抗活性表明这些残基可能参与受体识别/结合。
