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-inducin g peptide (DSIP) in the blood-brain barrier (BBB) is catalyzed by amin opeptidases. In this study, we have shown that peptidyl dipeptidase A in cultured bovine brain microvessel endothelial cells (BBMEC), a mode l of the BBB, and a purified form of this enzyme can also metabolize D SIP by sequential hydrolyses of dipeptides or tripeptides from the car boxyl terminus of this nonapeptide. Both the dipeptidase and tripeptid ase activity associated with peptidyl dipeptidase A can be inhibited b y 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). ( C) 1995 Academic Press, Inc.