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

Abstract

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 3.4.21.26)) 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.

• Authors: N Miura, S Shibata, S Watanabe
• Journal: Behavioural brain research (Behav Brain Res) Vol. 83 Issue 1-2 Pg. 213-6 (Feb 1997) ISSN: 0166-4328 [Print] Netherlands
• PMID: 9062687 (Publication Type: Journal Article)

Chemical References

• 1-(3-(2-indanylacetyl)-L-thioprolyl)pyrrolidine
• Pyrrolidines
• Serine Proteinase Inhibitors
• Arginine Vasopressin
• Serine Endopeptidases
• Prolyl Oligopeptidases

Topics

• Animals
• Arginine Vasopressin (pharmacology)
• Electric Stimulation
• Evoked Potentials (drug effects)
• Hippocampus (drug effects)
• In Vitro Techniques
• Male
• Prolyl Oligopeptidases
• Pyrrolidines (pharmacology)
• Rats
• Rats, Wistar
• Serine Endopeptidases (metabolism)
• Serine Proteinase Inhibitors (pharmacology)
• Stimulation, Chemical
• Synaptic Transmission (drug effects)