Taira K, Kaneto H
Nihon Yakurigaku Zasshi. 1987 May;89(5):243-52.
Prolyl endopeptidase (PPCE) plays an important role in the degradation of biologically active peptides such as vasopressin which facilitates the process of learning and memory. Here, the effect of synthetic PPCE inhibitors (Z-Pro-, Suc-Pro-, Suc-Pyr-, Suc-Sar- and Z-prolinal) on the acquisition and retention of avoidance response was studied. Using mice of the ddY strain, tests were performed both in repeated trials of an active avoidance task and in a newly contrived one-trial passive-active avoidance task. The applicability of both tests for the evaluation of the anti-amnesic effect of the drugs was confirmed by the effect of scopolamine and arginine vasopressin (AVP). The most potent inhibitor, Z-Pro-prolinal, facilitated the acquisition of active avoidance response and retarded the extinction of the response. Other inhibitors also facilitated the retention of the acquired response. In the one-trial passive-active avoidance test, the facilitating effect of the PPCE inhibitors on the acquisition was parallel to their activity as a PPCE inhibitor. Scopolamine-induced amnesia was also improved by the inhibitors. These results suggest that the anti-amnesic effect of PPCE inhibitors is partially attributed to their inhibitory effect on the breakdown of AVP in the brain.
脯氨酰内肽酶（PPCE）在诸如血管加压素等生物活性肽的降解过程中发挥着重要作用，而血管加压素有助于学习和记忆过程。在此，研究了合成的PPCE抑制剂（Z-脯氨酰-、琥珀酰-脯氨酰-、琥珀酰-吡咯酰-、琥珀酰-肌氨酰-和Z-脯氨醛）对回避反应的获得和保持的影响。使用ddY品系小鼠，在主动回避任务的重复试验以及新设计的单次被动-主动回避任务中进行了测试。东莨菪碱和精氨酸血管加压素（AVP）的作用证实了这两种测试对于评估药物抗遗忘作用的适用性。最有效的抑制剂Z-脯氨酰-脯氨醛促进了主动回避反应的获得并延缓了反应的消退。其他抑制剂也促进了已获得反应的保持。在单次被动-主动回避测试中，PPCE抑制剂对获得的促进作用与其作为PPCE抑制剂的活性平行。抑制剂也改善了东莨菪碱诱导的遗忘。这些结果表明，PPCE抑制剂的抗遗忘作用部分归因于它们对大脑中AVP分解的抑制作用。
