A study on the mechanism of mnemonic effect of vasopressin and vasopressin fragment analog

为了研究抗利尿激素及其片段类似物的作用机制，我们在行为学研究中考察了这些肽的记忆作用与谷氨酸受体之间的关系。NMDA受体拮抗剂或代谢性谷氨酸受体拮抗剂可抑制记忆任务的表现。与这些拮抗剂共同给药可降低肽的记忆作用。这些结果表明，肽的记忆作用归因于通过NMDA和/或I组代谢性谷氨酸受体的谷氨酸能神经元活性。并探讨了逆行神经递质与VPMF或NC的作用机制的关系。此外，我们还研究了环氧化酶（COX）抑制对肽诱导的记忆作用的影响，并在水迷宫训练后立即给予一些COX抑制剂。一种非特异性COX和一种特异性COX-2抑制剂，而非COX-1抑制剂。real - time PCR结果显示，COX-2抑制剂降低了大鼠脑内COX-2 mRNA的表达，但没有降低COX-1的表达，且COX-2 mRNA的表达在给药后2 h内降低。这些结果表明内源性COX-2激活是形成记忆的必要条件。与COX-2抑制剂共给药可降低多肽的助记作用，但与COX-1抑制剂不相同。这些观察结果，连同我们之前的发现，表明肽的V1A受体与Gq/11蛋白偶联；因此，V1A受体的激活诱导磷脂酶C、蛋白激酶C、磷脂酶A2的激活。因此，这些酶的激活可以引起内源性COX-2的激活，其产物（前列腺素E2）可能会诱导这些酶的信号转导进一步激活，因为前列腺素E2受体也与Gq/11蛋白偶联。少

In order to study the action mechanism of vasopressin or its fragment analog, we examined a relationship between the mnemonic effect of these peptides and glutamatergic receptor in the behavioral study. The administration of a NMDA receptor antagonist, or a metabotropic glutamate receptor antagonist, inhibited the performance in memory task. The mnemonic effect of the peptides was decreased by the co-administration with these antagonists. These results suggested that the mnemonic effect of the peptides attributed to the glutamatergic neuron activity via NMDA and/or group I metabotropic glutamate receptor.A relationship between retrograde neurotransmitter and action mechanism of VPMF or NC was also examined. Additionally, we investigated the influence of cyclooxygenase (COX) inhibition on mnemonic effect induced by the peptides, and some COX inhibitors were administrated immediately after the training in the water maze. A non-specific COX and a specific COX-2 inhibitors but not COX-1 in … More hibitor prolonged the latency in the water maze. The real time PCR showed that the administration of the COX-2 inhibitor decreased an appearance of COX-2 mRNA but not that of COX-1 in the brain, and the decrease of COX-2 mRNA was caused within 2 h after the administration of COX-2 inhibitor. These results suggested that endogenous COX-2 activation is needed to form the memory. The mnemonic effect of the peptides was decreased by the co-administration with the COX-2 inhibitor but not COX-1 inhibitor. These observations, together with our previous findings, suggest that the V1A receptors of the peptides are coupling with Gq/11 protein ; therefore, the activation of the V1A receptors induces activation of phospholipase C, protein kinase C, phospholipase A2. Consequently, these enzyme activations could cause the activation of endogenous COX-2, and the products (prostaglandin E2) may induce further activation of signal transduction of the enzymes, since prostaglandin E2 receptor is also coupled with Gq/11 protein. Less