Presence of an endogenous inhibitor of dipeptidyl carboxypeptidase in rat brain

Whole rat brain dipeptidyl carboxypeptidase (E.C. 3.4.15.1) was heterogeneously distributed among 10 brain regions studied. In corpus striatum, the enzyme was enriched in the P₂ pellet, a subfraction high in myelin and nerve terminals. Using [³H]benzoylphenylalanyl-alanyl-proline as a substrate, dipeptidyl carboxypeptidase manifested a different anion requirement than has been reported for other substrates. Endogenous inhibitors of the enzyme were found in corpus striatum and could be removed by dialysis or Sephadex G25 chromatography. Boiled striatal cytosol inhibited membrane-bound enzyme activity in a concentration-dependent manner and confirmed the presence of an endogenous soluble, heat-stable inhibitor in rat brain. The inhibitor apparently could be degraded by a component of the striatal P₂ membranes. The inhibitor was present in all 10 brain regions studied and its levels did not appear to be related to the specific activity of dipeptidyl carboxypeptidase. Potential mechanisms for biological regulation of dipeptidyl carboxypeptidase activity are discussed in light of the above findings.