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 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.
Miura
N
N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, Fukuoka, Japan.
Shibata
S
S
Watanabe
S
S
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D000085822:Prolyl Oligopeptidases; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects*
C106522:1-(3-(2-indanylacetyl)-L-thioprolyl)pyrrolidine; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D001127:Arginine Vasopressin; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases