Elsevier

Peptides

Volume 5, Issue 5, September–October 1984, Pages 857-860
Peptides

Cyclic hexa- and pentapeptide somatostatin analogues with reduced gastric inhibitory activity

https://doi.org/10.1016/0196-9781(84)90106-2Get rights and content

Abstract

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 μg 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 (∼50%) and pepsin (∼85%) secretions, but the inhibition was not dose-related being similar with doses of 10 to 50 μg 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 <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.

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2

On leave from: Department of Biochemistry, School of Medicine, University de Alcala de Henares, Alcala de Henares, Madrid, Spain.

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