Title
Kinetic study of neuropeptide Y (NPY) proteolysis in blood and identification of <tex>NPY$_{3-35}$</tex>: a new peptide generated by plasma kallikrein Kinetic study of neuropeptide Y (NPY) proteolysis in blood and identification of <tex>NPY$_{3-35}$</tex>: a new peptide generated by plasma kallikrein
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Baltimore, Md ,
Subject
Pharmacology. Therapy
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Volume/pages
284(2009) :37 , p. 24715-24724
ISSN
0021-9258
ISI
000269734000006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
There is little information on how neuropeptide Y (NPY) proteolysis by peptidases occurs in serum, in part because reliable techniques are lacking to distinguish different NPY immunoreactive forms and also because the factors affecting the expression of these enzymes have been poorly studied. In the present study, LC-MS/MS was used to identify and quantify NPY fragments resulting from peptidolytic cleavage of NPY136 upon incubation with human serum. Kinetic studies indicated that NPY136 is rapidly cleaved in serum into 3 main fragments with the following order of efficacy: NPY336 &#8811; NPY335 > NPY236. Trace amounts of additional NPY forms were identified by accurate mass spectrometry. Specific inhibitors of dipeptidyl peptidase IV, kallikrein, and aminopeptidase P prevented the production of NPY336, NPY335, and NPY236, respectively. Plasma kallikrein at physiological concentrations converted NPY336 into NPY335. Receptor binding assays revealed that NPY335 is unable to bind to NPY Y1, Y2, and Y5 receptors; thus NPY335 may represent the major metabolic clearance product of the Y2/Y5 agonist, NPY336.
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