Chronic treatment with the uncompetitive NMDA receptor antagonist memantine influences the polyamine and glycine binding sites of the NMDA receptor complex in aged rats.

I Bresink, W Danysz, C G Parsons, P Tiedtke, E Mutschler
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引用次数: 18

Abstract

Receptor binding studies on rat cortical membranes were used to characterize the NMDA receptor in aged rats (22 months) treated for 20 months with a memantine containing diet delivering 30 mg/kg/day in comparison to aged and young/adult rats treated with control-diet. Spatial memory impairing effects of (+)-MK-801 (0.16 mg/kg) in the radial maze was not altered within the course of memantine-treatment (up to 16 months). However, chronic memantine-treatment significantly increased the number of [3H]MK-801 binding sites and the affinity of [3H]glycine. A non-significant trend to such changes was also seen in aged-control rats. Glycine-dependent [3H]MK-801 binding (functional binding under non-equilibrium conditions at a fixed L-glutamate concentration) revealed that a decreased ability of glycine to stimulate channel opening in aged rats was partially attenuated by the long-term memantine treatment. Furthermore, an increased ability of spermidine to enhance [3H]MK-801 binding in aged-control rats was even more pronounced in the aged memantine-treated group. Together these findings may indicate that changes in functional receptor-channel properties during the process of aging occur prior to a detectable loss of binding sites and that memantine enhances an endogenous compensatory mechanism triggered by glutamatergic hypofunction which is suggested to take place in aging.

非竞争性NMDA受体拮抗剂美金刚慢性治疗影响老年大鼠NMDA受体复合物的多胺和甘氨酸结合位点。
通过对大鼠皮质膜的受体结合研究,研究了老年大鼠(22个月)在20个月的时间里,与对照组大鼠和年轻/成年大鼠相比,在含有30mg /kg/天的美金刚饮食中治疗NMDA受体。(+)-MK-801 (0.16 mg/kg)在径向迷宫中的空间记忆损害作用在美刚胺治疗过程中(长达16个月)没有改变。然而,慢性美金刚治疗显著增加了[3H]MK-801结合位点的数量和[3H]甘氨酸的亲和力。在老龄对照大鼠中也发现了这种变化的不显著趋势。甘氨酸依赖[3H]MK-801结合(固定l -谷氨酸浓度下非平衡条件下的功能结合)表明,甘氨酸刺激老年大鼠通道打开能力的下降被长期美金刚处理部分减弱。此外,亚精胺增强衰老对照大鼠[3H]MK-801结合的能力在老年美金刚处理组中更为明显。总之,这些发现可能表明,在衰老过程中,功能受体通道特性的变化发生在可检测到的结合位点丢失之前,并且美金刚增强了由谷氨酸功能减退引发的内源性代偿机制,这被认为发生在衰老过程中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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