Increase in the septal vasopressin content by prolyl endopeptidase inhibitors in rats.

Prolyl endopeptidase (PEP; EC 3.4.21.26) cleaves the Pro-Arg bond of arginine-vasopressin (AVP). This study investigated the effects of PEP inhibitors, 1-[1-(benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-prolinal) and 1-[3-(2-indanylacetyl)-L-thioprolyl]pyrrolidine (Z-321), on the AVP content in the septum of rats. Oral administration of Z-Pro-prolinal (100 mg/kg) and Z-321 (100 mg/kg) significantly increased the septal AVP content. At 10 mg/kg, Z-321 slightly increased the content. In contrast, the D-thioprolyl form of Z-321 (100 mg/kg), which lacks an inhibitory effect on the enzyme, failed to affect the AVP content. These results indicate that PEP inhibitors increase the content of AVP through inhibition of the enzyme activity in vivo. Therefore, it is suggested that PEP may contribute to the degradation of endogenous AVP in the brain.