Structure-activity relationship of some analogues of gastrin and cholecystokinin on intestinal smooth muscle of the guinea-pig

E. S. Vizi, G. Bertaccini, Marianina Impicciatore, P. Mantovani, J. Zséli, J. Knoll

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Abstract

The structure-activity relationship of gastrin- and cholecystokinin like polypeptides has been studied on intestinal smooth muscle of the guinea pig. The polypeptides studied here elicited reciprocal responses of the two muscle layers of ileum similar to the responses to electrical stimulation. The contraction of the longitudinal muscle and the relaxation of the circular muscle layer in response to peptides was followed by a contraction of circular muscle and a relaxation of longitudinal muscle. 1. These alternating contractions of the two muscle layers were inhibited by tetrodotoxin (10-6 M). Hexamethonium (8.2×10-4 M) prevented the responses of the circular muscle to polypeptides indicating that at least one ganglion is involved in the nervous pathway running to the circular muscle. 2. On the longitudinal muscle strip of guinea-pig ileum the contractions produced by polypeptides were dose-dependent. From the structure-activity relationship study it seems that the presence of tyrosine-O-sulphate is important for effective interaction between the peptides and the peptide-sensitive receptors of the ganglion cells of the Auerbach plexus. The desulphated form of peptides and peptides with only few amino acid sequences proved to be much less active. 3. There was tachyphylaxis when these peptides were applied in concentrations two or three times higher than their maximally effective concentration.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume284
Issue number3
DOIs
Publication statusPublished - Sep 1 1974

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Keywords

  • Cholecystokinin
  • Desensitization
  • Gastrin
  • Intestinal-motility

ASJC Scopus subject areas

  • Pharmacology

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