Neurotensin-metabolizing peptidases in rat fundus plasma membranes.
The mechanisms by which neurotensin (NT) was inactivated by rat fundus plasma membranes were characterized. Primary inactivating cleavages occurred at the Arg8-Arg9, Pro10-Tyr11, and Ile12-Leu13 peptidyl bonds. Hydrolysis at the Arg8-Arg9 bond was fully abolished by the use of N-[1(R,S)-carboxy-2-phenylethyl]-alanyl-alanyl-phenylalanine-p- aminobenzoate, a result indicating the involvement at this site of a recently purified soluble metallopeptidase. Hydrolysis of the Pro10-Tyr11 bond was totally resistant to N-benzyloxycarbonyl-prolyl-prolinal and thiorphan, an observation suggesting that the peptidase responsible for this cleavage was different from proline endopeptidase and endopeptidase 24.11 and might correspond to a NT-degrading neutral metallopeptidase recently isolated from rat brain synaptic membranes. The enzyme acting at the Ile12-Leu13 bond has not yet been identified. Secondary cleavages occurring on NT degradation products were mainly generated by bestatin-sensitive aminopeptidases and post-proline dipeptidyl aminopeptidase. The content in NT-metabolizing peptidases present in rat fundus plasma membranes is compared with that previously established for purified rat brain synaptic membranes.
Checler
F
F
Barelli
H
H
Kwan
C Y
CY
Kitabgi
P
P
Vincent
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D005748:Gastric Fundus / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D011480:Protease Inhibitors; D009496:Neurotensin; D002216:Captopril; D010447:Peptide Hydrolases