title: Pathway of inactivation of cholecystokinin octapeptide (CCK-8) by synaptosomal fractions.
abstract: Cholecystokinin octapeptide (CCK-8) was degraded by peptidases present in intact synaptosomes isolated from rat cortex and hypothalamus. Most of the degrading activity was present in the cytoplasmic fraction although a small amount (7%) was membrane-bound. Products of the degradation were isolated by HPLC and characterized by amino acid analysis. The Met(3)-Gly(4) bond was the main primary site of cleavage giving rise to Asp-Tyr(SO(3)H)-Met and Gly-Trp-Met-Asp-Phe-NH(2). These products appeared to be further degraded by sequential removal of amino-terminal residues. The Asp(1)-Tyr(2) and Asp(7)-Phe(8) bonds were also sites of cleavage. p-Chloromercuribenzoate was the most effective inhibitor (90% inhibition) of CCK-8 degradation by synaptosomal peptidases at the concentrations tested. This peptidase activity in synaptosomes may be important in the regulation of levels of the neuropeptide CCK-8 at the synapse. Identification of the sites of cleavage of CCK-8 on incubation with synaptosomes will assist in the isolation and characterization of the enzymes involved.
authors.affiliation: MRC Neuroendocrinology Unit, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne NE4 6BE, England.
authors.forename: J R
authors.initials: JR
authors.lastname: McDermott
authors.forename: P R
authors.initials: PR
authors.lastname: Dodd
authors.forename: J A
authors.initials: JA
authors.lastname: Edwardson
authors.forename: J A
authors.initials: JA
authors.lastname: Hardy
authors.forename: A I
authors.initials: AI
authors.lastname: Smith