Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Aminopeptidases
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Animals
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Base Sequence
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Catalysis
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Cell Membrane / enzymology
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Cerebral Cortex / enzymology
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Cholecystokinin / antagonists & inhibitors*
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DNA
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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Humans
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Hydrolysis
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Indoles / chemical synthesis
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Indoles / pharmacology
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Mice
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Molecular Sequence Data
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Peptide Fragments / metabolism
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / metabolism
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Rats
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Sequence Homology, Amino Acid
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Serine Endopeptidases / chemical synthesis
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Serine Endopeptidases / isolation & purification
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Serine Endopeptidases / metabolism*
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Substrate Specificity
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Type C Phospholipases / metabolism
Substances
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Indoles
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Peptide Fragments
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Protease Inhibitors
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butabindide
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DNA
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Cholecystokinin
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Type C Phospholipases
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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tripeptidyl-peptidase 2
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Serine Endopeptidases