Effects of analogs of (pyro)Glu-His-Gly-OH on food consumption and gastric acid secretion in rats.
ABSTRACT The effects of administration of (pyro)Glu-His-Gly-OH and its analogs on food consumption and 2-Deoxy-D-Glucose (2-DG)-induced gastric acid secretion were examined in rats. (Pyro)Glu-His-Gly-OH and (pyro)Glu-His-EA significantly reduced food consumption, but not gastric acid secretion as compared with controls. The tripeptides: (pyro)Glu-3Me-His-Gly-OH, (pyro)Glu-His-D-Ala-OH, and (pyro)Glu-Phe-Gly-OH were found to significantly inhibit 2-DG-induced gastric acid secretion. Our results indicate that some analogs of (pyro)Glu-His-Gly-OH cause a greater inhibition of food consumption or gastric acid secretion in rats than the original tripeptide, in analogy to findings obtained in dogs.
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ABSTRACT: 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.International journal of peptide and protein research 10/1990; 36(3):267-74.