Products of cholecystokinin (CCK)-octapeptide proteolysis interact with central CCK receptors

L. Steardo, M. Knight, C. A. Tamminga, T. N. Chase

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Peptidases present in central nervous system (CNS) synaptic membranes, hydrolyze the neuroactive peptide cholecystokinin-octapeptide (CCK-8; Asp-Tyr-SO3H-Met-Gly-Trp-Met-Asp-Phe-NH2). In order to determine the pathway of degradation, synthetic CCK-8 was incubated at 37°C with purified synaptic membranes; at various intervals reaction samples were removed from the reaction mixture and analysed by high-performance liquid chromatography to identify and quantify the peptide fragments. The results indicate an initial endopeptidase cleavage at the Met-Gly bond producing CCK-5 (Gly-Trp-Met-Asp-Phe-NH2). The carboxyl-terminal pentapeptide is further proteolysed to CCK-4 (Trp-Met-Asp-Phe-NH2) by a puromycin-sensitive aminopeptidase and to CCK-3 (Met-Asp-Phe-NH2) and Gly-Trp by an endopeptidase action, CCK-3 and CCK-2 appear to be relatively stable end-products. Moreover, these proteolytic fragments are shown to bind to the CCK receptor in brain with varying potencies.

Original languageEnglish (US)
Pages (from-to)319-325
Number of pages7
JournalNeuroscience Letters
Volume54
Issue number2-3
DOIs
StatePublished - Jan 1 1985

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Keywords

  • cholecystokinin antagonist
  • degradation pathway
  • neuropeptidases
  • neuropeptides

ASJC Scopus subject areas

  • Neuroscience(all)

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