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 Citations (Scopus)

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
StatePublished - 1985

Fingerprint

Cholecystokinin Receptors
Sincalide
Cholecystokinin
Proteolysis
Synaptic Membranes
Endopeptidases
methionylglycine
aspartyltyrosine
Tetragastrin
Peptide Fragments
Peptide Hydrolases
Central Nervous System
High Pressure Liquid Chromatography
Peptides
Brain
cholecystokinin 8
cholecystokinin pentapeptide

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Products of cholecystokinin (CCK)-octapeptide proteolysis interact with central CCK receptors. / Steardo, L.; Knight, M.; Tamminga, C. A.; Chase, T. N.

In: Neuroscience Letters, Vol. 54, No. 2-3, 1985, p. 319-325.

Research output: Contribution to journalArticle

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