Miura N, Shibata S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, Fukuoka, Japan.
Behav Brain Res. 1997 Feb;83(1-2):213-6. doi: 10.1016/s0166-4328(97)86072-x.
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.
本研究调查了精氨酸加压素（AVP）和脯氨酰内肽酶（PEP；EC 3.4.21.26）抑制剂（1-[3-(2-茚满基乙酰基)-L-硫代脯氨酰]吡咯烷（Z-321），其在体外可降解AVP）对与弱强直刺激相关的场兴奋性突触后电位（EPSP）的短时程增强的影响。在大鼠海马切片的CA1区记录经电刺激Schaffer侧支/联合通路后的EPSP。10^(-8) M的AVP和10^(-4) M的Z-321增强了弱强直刺激诱导的增强作用；EPSP的强直后增强幅度增大，且增强持续60分钟。相比之下，Z-321的外消旋D-硫代脯氨酰化合物对PEP几乎没有任何抑制作用，在10^(-4) M时未能影响增强作用。Z-321的促进作用可被AVP V1受体拮抗剂[d(CH2)5,Tyr(Me)2]AVP（10^(-8) M）的应用所逆转，这表明Z-321的作用是通过V1受体介导的。这些发现表明，Z-321由于其对PEP降解AVP的抑制作用而增强了增强作用。
