Characterization and inhibition of a cholecystokinin-inactivating serine peptidase.
A cholecystokinin (CCK)-inactivating peptidase was purified and identified as a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10), a cytosolic subtilisin-like peptidase of previously unknown functions. The peptidase was found in neurons responding to cholecystokinin, as well as in non-neuronal cells. Butabindide, a potent and specific inhibitor, was designed and shown to protect endogenous cholecystokinin from inactivation and to display pro-satiating effects mediated by the CCKA receptor.
Rose
C
C
Unité de Neurobiologie et Pharmacologie de l'INSERM, Centre Paul Broca, Paris, France.
Vargas
F
F
Facchinetti
P
P
Bourgeat
P
P
Bambal
R B
RB
Bishop
P B
PB
Chan
S M
SM
Moore
A N
AN
Ganellin
C R
CR
Schwartz
J C
JC
D000595:Amino Acid Sequence; D000626:Aminopeptidases; D000818:Animals; D001483:Base Sequence; D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004247:DNA; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D006801:Humans; D006868:Hydrolysis; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism
D007211:Indoles; D010446:Peptide Fragments; D011480:Protease Inhibitors; C098807:butabindide; D004247:DNA; D002766:Cholecystokinin; D010738:Type C Phospholipases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases