Effects of prolyl endopeptidase inhibitors and neuropeptides on delayed neuronal death in rats.
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.
Shishido
Y
Y
Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan. byg00625@nifty.ne.jp
Furushiro
M
M
Tanabe
S
S
Shibata
S
S
Hashimoto
S
S
Yokokura
T
T
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000085822:Prolyl Oligopeptidases; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism*
D004151:Dipeptides; D004791:Enzyme Inhibitors; C105467:N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylacetal; D017483:Receptors, Vasopressin; D013844:Thiazoles; D014667:Vasopressins; C038541:N-benzyloxycarbonylprolylprolinal; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases