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

Abstract

We investigated the effects of the prolyl endopeptidase inhibitors 1-[1-(Benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-Prolinal) and N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA) on delayed neuronal death induced by four-vessel-occlusion transient ischemia in rats. We also examined the effects of [pGlu4, Cyt6, ArgS]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.

• Authors: Y Shishido, M Furushiro, S Tanabe, S Shibata, S Hashimoto, T Yokokura
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 372 Issue 2 Pg. 135-42 (May 14 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10395093 (Publication Type: Journal Article)

Chemical References

• Dipeptides
• Enzyme Inhibitors
• N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylacetal
• Receptors, Vasopressin
• Thiazoles
• Vasopressins
• N-benzyloxycarbonylprolylprolinal
• Serine Endopeptidases
• Prolyl Oligopeptidases

Topics

• Animals
• Cell Death (drug effects)
• Dipeptides (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Male
• Neurons (drug effects, metabolism, pathology)
• Prolyl Oligopeptidases
• Rats
• Rats, Wistar
• Receptors, Vasopressin (metabolism)
• Serine Endopeptidases (metabolism)
• Thiazoles (pharmacology)
• Vasopressins (metabolism)