Effects of prolyl endopeptidase inhibitors and neuropeptides on delayed neuronal death in rats

Yoshiyuki Shishido*, Masayoshi Furushiro, Shuichi Tanabe, Shigenobu Shibata, Shusuke Hashimoto, Teruo Yokokura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


We investigated the effects of the prolyl endopeptidase inhibitors 1-[1-(Benzyloxycarbonyl)-l-prolyl]prolinal (Z-Pro-Prolinal) and N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylacetal (ZTTA) on delayed neuronal death induced by four-vessel-occlusion transient ischemia in rats. We also examined the effects of [pGlu4, Cyt6, Arg8]vasopressin (vasopressin-(4-9)) and thyrotropin-releasing hormone (TRH) on the delayed neuronal death. Furthermore, we investigated the role of vasopressin receptors in the effects of vasopressin and prolyl endopeptidase inhibitors. Z-Pro-Prolinal, vasopressin-(4-9) and TRH protected pyramidal cells in the CA1 subfield of the rat hippocampus from delayed neuronal death after 10-min ischemia. The effect of vasopressin-(4-9) was abolished by vasopressin receptor antagonists. The effect of Z-Pro-Prolinal was also abrogated by the antagonists. These results suggest that the neuroprotective effect of prolyl endopeptidase inhibitors is mediated by neuropeptides such as [Arg8]vasopressin and TRH, and indicate the involvement of vasopressin receptors in the neuroprotective effect of vasopressin-(4-9) and prolyl endopeptidase inhibitors. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2
Publication statusPublished - 1999 May 14


  • Ischemia
  • Neuronal death, delayed
  • Prolyl endopeptidase inhibitor
  • Pyramidal cell
  • Vasopressin-(4-9)
  • Z-Pro-Prolinal
  • ZTTA (N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylacetal)

ASJC Scopus subject areas

  • Pharmacology


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