Z-321, a prolyl endopeptidase inhibitor, augments the potentiation of synaptic transmission in rat hippocampal slices.

The present study investigated the effects of arginine-vasopressin (AVP) and (1-[3-(2-indanylacetyl)-L-thioprolyl] pyrrolidine (Z-321), an inhibitor of prolyl endopeptidase (PEP; (EC which degrades AVP in vitro, on the short-lasting potentiation of the field excitatory postsynaptic potentials (EPSP) coupled with a weak tetanus. The EPSP, after the electrical stimulation of the Schaffer collateral/commissural pathway, were recorded in the CA1 region of rat hippocampal slices. AVP at 10(-8) M and Z-321 at 10(-4) M augmented the potentiation induced by the weak tetanus; the magnitude of the post-tetanic potentiation of the EPSP was enhanced and the potentiation lasted for 60 min. In contrast, the racemic D-thioprolyl compound of Z-321, which virtually lacks any inhibitory effects on PEP, failed to affect the potentiation at 10(-4) M. The facilitatory effect of Z-321 was reversed by the application of [d(CH2)5,Tyr(Me)2]AVP (10(-8) M), an antagonist of the AVP V1 receptors, indicating that the effect of Z-321 was mediated through the V1 receptors. These findings suggest that Z-321 augmented the potentiation due to its inhibitory influence on the AVP degradation by PEP.
AuthorsN Miura, S Shibata, S Watanabe
JournalBehavioural brain research (Behav Brain Res) Vol. 83 Issue 1-2 Pg. 213-6 (Feb 1997) ISSN: 0166-4328 [Print] NETHERLANDS
PMID9062687 (Publication Type: Journal Article)
Chemical References
  • 1-(3-(2-indanylacetyl)-L-thioprolyl)pyrrolidine
  • Pyrrolidines
  • Serine Proteinase Inhibitors
  • Arginine Vasopressin
  • Serine Endopeptidases
  • prolyl oligopeptidase
  • Animals
  • Arginine Vasopressin (pharmacology)
  • Electric Stimulation
  • Evoked Potentials (drug effects)
  • Hippocampus (drug effects)
  • In Vitro Techniques
  • Male
  • Pyrrolidines (pharmacology)
  • Rats
  • Rats, Wistar
  • Serine Endopeptidases (metabolism)
  • Serine Proteinase Inhibitors (pharmacology)
  • Stimulation, Chemical
  • Synaptic Transmission (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: