Characterization of a serine peptidase responsible for the inactivation of endogenous cholecystokinin in human brain.
Depolarization of slices of human cerebral cortex releases cholecystokinin-8 immunoreactivity, only a fraction of which is recovered in intact immunoreactive form in the medium. This suggests that extensive hydrolysis takes place during short incubations. In the presence of diisopropylfluorophosphate, a serine reagent, the recovery is nearly doubled, however, consistent with the involvement of a serine peptidase activity. The latter was characterized by assessing the protective effects of a series of serine protease inhibitors belonging to the families of peptide chloromethylketones or boronic acids. The relative potency of these inhibitors was similar to corresponding values previously found with rat brain slices indicating that a similar serine peptidase activity is responsible for endogenous cholecystokinin inactivation in the two species.
Rose
C
C
Unité de Neurobiologie et Pharmacologie (U. 109) de l'INSERM, Centre Paul Broca, Paris, France.
Vargas
F
F
Silhouette
B
B
Devaux
B
B
Schwartz
J C
JC
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology*; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D012697:Serine Endopeptidases / Q000502:physiology*; D015843:Serpins / Q000494:pharmacology; D012844:Sincalide / Q000378:metabolism*; D015244:Thiorphan / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D015843:Serpins; D007531:Isoflurophate; D015244:Thiorphan; D000626:Aminopeptidases; D012697:Serine Endopeptidases; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; D012844:Sincalide