CCK26-33 degrading activity in brain and nonneural tissue: a metalloendopeptidase.
Cholecystokinin octapeptide (CCK26-33) is metabolized by neural membranes with an initial cleavage to CCK29-33 and subsequent breakdown to CCK31-33 and CCK32-33; this pattern of proteolysis occurs on incubation with either P2 or purified lysed synaptosomal membranes. To determine whether the pattern of CCK26-33 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 CCK29-33 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 CCK29-33 formation requires a metal ion and sulfydryl 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 CCK26-33 that is cleaved by this enzyme.
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008666:Metalloendopeptidases; D010179:Pancreas / Q000201:enzymology; D011480:Protease Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000031:analogs & derivatives* / Q000378:metabolism; D013570:Synaptic Membranes / Q000201:enzymology*
D011480:Protease Inhibitors; C044201:cholecystokinin (26-33); D010450:Endopeptidases; D008666:Metalloendopeptidases; D012844:Sincalide