Cholecystokinin octa- and tetrapeptide degradation by synaptic membranes. III. Inactivation of CCK-8 by a phosphoramidon-sensitive endopeptidase.
Solubilization of rat synaptic membranes by Triton X-100 followed by DEAE-cellulose chromatography allowed the separation of a phosphoramidon-sensitive endopeptidase that cleaved CCK-8. This enzymatic activity revealed similar if not identical to "enkephalinase A." A major cleavage point, at the Trp30-Met31 bond, and a minor one at the Tyr27-Met28 bond were identified in the sequence of CCK-8. Replacements of the Met28 and Met31 residues by Thr and either Leu or Nle respectively, in CCK-9 analogues, did not improve the resistance of these peptides to enzymatic degradation. The regional distribution in rat brain of this CCK-8 cleaving endopeptidase displayed marked variations with the highest activity in striatal membranes; it closely followed that described for "enkephalinase" in mouse brain.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D005755:Gastrins / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology*; D007700:Kinetics; D015260:Neprilysin; D011480:Protease Inhibitors; D051381:Rats; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013570:Synaptic Membranes / Q000201:enzymology*; D013758:Tetragastrin / Q000378:metabolism*; D014018:Tissue Distribution
D005755:Gastrins; D006020:Glycopeptides; D011480:Protease Inhibitors; D013758:Tetragastrin; D015260:Neprilysin; D012844:Sincalide; C008890:phosphoramidon