Inhibition of Sham Feeding-Induced Gastric Secretion and Serum Hormonal Responses by Analogs of (pyro)Glu-His-Gly-OH

The effects of intravenous infusion of analogs of (pyro)Glu-His-Gly-OH on secretion of gastric acid and elevation of serum gastrin and insulin levels induced by sham feeding were evaluated in conscious dogs. Tripeptides (pyro)Glu-3Me-His-Gly-OH, (pyro)Glu-His-D-Ala-OH, D-(pyro)Glu-His-Gly-OH, (pyro)Glu-His-Trp-NH₂, (pyro)Glu-His-Gly-NH₂, and (pyro)Glu-His-Gly-ethylamide, but not control peptides Glu-His-Pro-OH or Leu-Arg-Phe-OH, significantly suppressed the cephalic phase rise in serum insulin and gastrin as compared to saline-infused controls and lowered these hormonal levels below basal values. Analogs (pyro)Glu-3Me-His-Gly-OH, D-(pyro)Glu-His-Gly-OH, and (pyro)Glu-His-D-Ala-OH also significantly inhibited the gastric acid response to sham feeding. The reductions in gastric acid caused by (pyro)Glu-His-Gly-NH₂ or (pyro)Glu-His-Gly-ethylamide were less intense. Statistical analyses of food intake in 86 sham feeding experiments in seven dogs showed that the reduction during the infusion of (pyro)Glu-His-Gly-OH and its analogs was not significant by Duncan's multiple range test, and only that induced in (pyro)Glu-3Me-His-Gly-OH was significant by Student's t-test as compared to saline control. Our findings suggest that some analogs of (pyro)Glu-His-Gly-OH are more powerful inhibitors of the hormonal and gastric secretory responses during the cephalic phase stimulation than the original tripeptide.