Rao V L, Agrawal A K, Murthy C R
School of Life Sciences, University of Hyderabad, India.
Neurosci Lett. 1991 Sep 16;130(2):251-4. doi: 10.1016/0304-3940(91)90408-l.
Binding of glutamate and muscimol (an agonist for GABAA receptors) to their respective receptors has been studied in the cerebellum of normal and hyperammonemic rats. There was a decrease in both high- and low-affinity binding of glutamate in the cerebellum during hyperammonemia. Kinetic studies revealed that the decrease is due to a reduction in the number of binding sites, but not due to changes in the binding affinities. Further studies also revealed that the decrease was only in the N-methyl-D-aspartate (NMDA)-specific binding sites without any alterations in the binding to non-NMDA sites represented by kianic acid (KA)- and quisqualic acid (QQ)-sensitive receptor sites. These effects were also mimicked when the membrane preparations from the cerebellum of normal animals were incubated with ammonium acetate. Enhancement of muscimol binding was observed in animals injected with ammonium acetate. It is concluded that hyperammonemic states, even in the presence of a functional liver, are capable of altering amino acid neurotransmission and this might play an important role in cerebral dysfunction under these conditions.
在正常和高氨血症大鼠的小脑中，已对谷氨酸和蝇蕈醇（一种GABAA受体激动剂）与其各自受体的结合情况进行了研究。高氨血症期间，小脑中谷氨酸的高亲和力和低亲和力结合均减少。动力学研究表明，这种减少是由于结合位点数量的减少，而非结合亲和力的变化。进一步研究还发现，减少仅发生在N-甲基-D-天冬氨酸（NMDA）特异性结合位点，而以犬尿喹啉酸（KA）和quisqualic酸（QQ）敏感受体位点为代表的非NMDA位点的结合没有任何改变。当将正常动物小脑的膜制剂与醋酸铵一起孵育时，也会出现这些效应。在注射醋酸铵的动物中观察到蝇蕈醇结合增强。得出的结论是，即使在肝功能正常的情况下，高氨血症状态也能够改变氨基酸神经传递，这可能在这些情况下的脑功能障碍中起重要作用。
