CCK26-33 degrading activity in brain and nonneural tissue: A metalloendopeptidase

L. Steardo, M. Knight, C. A. Tamminga

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cholecystokinin octapeptide (CCK[26-33]) is metabolized by neural membranes with an initial cleavage to CCK[29-33] and subsequent breakdown to CCK[31-33] and CCK[32-33]; this pattern of proteolysis occurs on incubation with either P2 or purified lysed synaptosomal membranes. To determine whether the pattern of CCK[26-33] proteolysis is unique to the brain and whether regional brain differences in its pathway or rate exist, we analyzed the proteolysis of CCK by synaptic membranes of various brain areas and cellular membranes of peripheral tissue. The pattern of degradation in brain did not differ among the regions studied. The overall proteolysis rate, as measured by the formation of tryptophan, was higher in the striatum than in the cortex, although CCK[29-33] was formed at the same rate in both areas. In nonneural tissue, the rate of degradation was highest in liver membranes and lowest in pancreatic acinar cell preparations. Thus, it appears that degradative peptidases are not necessarily colocalized with CCK receptors. The pattern of product formation is the same in peripheral compared with CNS membranes; thus, the degradative pathway does not appear to be unique to brain tissue. The enzyme present in synaptic membranes that is responsible for CCK[29-33] formation requires a metal ion and sulfhydryl groups for the catalysis and thus is a metalloendopeptidase. Furthermore, its activity is inhibited by Ac-Gly-Phe-Nle-al, a peptide aldehyde whose sequence bears some homology to the amino acid sequence in the region of CCK[26-33] that is cleaved by this enzyme.

Original languageEnglish (US)
Pages (from-to)784-790
Number of pages7
JournalJournal of Neurochemistry
Volume45
Issue number3
StatePublished - 1985

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Metalloendopeptidases
Cholecystokinin
Brain
Proteolysis
Tissue
Membranes
Synaptic Membranes
glycylphenylalanine
Cholecystokinin Receptors
Amino Acid Sequence Homology
Sincalide
Acinar Cells
Enzymes
Catalysis
Aldehydes
Tryptophan
Degradation
Peptide Hydrolases
Metals
Ions

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

CCK26-33 degrading activity in brain and nonneural tissue : A metalloendopeptidase. / Steardo, L.; Knight, M.; Tamminga, C. A.

In: Journal of Neurochemistry, Vol. 45, No. 3, 1985, p. 784-790.

Research output: Contribution to journalArticle

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