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.
Augustijns. P F PF; Ng. K Y KY; Williams. T M TM; Borchardt. R T RT
Key Findings
- Peptidyl dipeptidase A in brain endothelial cells cuts DSIP from the tail end, reducing its availability.
- Captopril, a known ACE‑inhibitor, blocks both the dipeptidase and tripeptidase actions of peptidyl dipeptidase A.
- Combining captopril with an aminopeptidase blocker such as bestatin completely prevents DSIP breakdown in the BBB model.
Practical Outcomes
- If you’re using DSIP for sleep or performance, co‑administering an ACE‑inhibitor like captopril (under medical supervision) and an aminopeptidase inhibitor could keep more of the peptide active in the brain. However, these drugs have other effects and aren’t typically used for this purpose, so safety and dosing need careful consideration.
Summary
The study shows that the brain‑protective peptide DSIP gets broken down by an enzyme called peptidyl dipeptidase A at the blood‑brain barrier, but this breakdown can be stopped by drugs that block that enzyme (like captopril) and another class of enzymes (using bestatin). In simple terms, DSIP doesn’t stay intact in the brain unless you add specific inhibitors.
Abstract
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).
Study Information
pubmed
1995
1995-05-25T00:00:00.000Z
10.1006/bbrc.1995.1754