Peptidyl dipeptidase A-catalyzed metabolism of delta sleep-inducing peptide in bovine brain microvessel endothelial cells: a cell culture model of the blood brain barrier.
Previous studies have shown that the metabolism of delta sleep-inducing peptide (DSIP) in the blood-brain barrier (BBB) is catalyzed by amino-peptidases. In this study, we have shown that peptidyl dipeptidase A in cultured bovine brain microvessel endothelial cells (BBMEC), a model of the BBB, and a purified form of this enzyme can also metabolize DSIP by sequential hydrolyses of dipeptides or tripeptides from the carboxyl terminus of this nonapeptide. Both the dipeptidase and tripeptidase activity associated with peptidyl dipeptidase A can be inhibited by captopril. Total stabilization of DSIP to metabolism in BBMEC could be achieved by inclusion of an inhibitor of peptidyl dipeptidase A (e.g., captopril) and an inhibitor of aminopeptidases (e.g., bestatin).
Augustijns
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PF
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045, USA.
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Williams
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TM
Borchardt
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RT
D000595:Amino Acid Sequence; D000818:Animals; D001812:Blood-Brain Barrier; D002417:Cattle; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D002851:Chromatography, High Pressure Liquid; D003701:Delta Sleep-Inducing Peptide / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D008833:Microcirculation; D008955:Models, Cardiovascular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D007703:Peptidyl-Dipeptidase A / Q000302:isolation & purification / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D010446:Peptide Fragments; D003701:Delta Sleep-Inducing Peptide; D007703:Peptidyl-Dipeptidase A