Kessler M, Baudry M, Cummins J T, Way S, Lynch G
J Neurosci. 1986 Feb;6(2):355-63. doi: 10.1523/JNEUROSCI.06-02-00355.1986.
The number of Na+-independent, Cl--dependent glutamate binding sites in rat hippocampal membranes is increased two- to fourfold after pre-exposing isolated membranes or hippocampal slices to high concentrations (0.1-10 mM) of L-glutamate or of glutamate analogs with high affinity for this binding site, such as quisqualate, homocysteate, or aminoadipate. N-Methylaspartate and kainate are ineffective. A similar binding increase is induced by transient exposure to the dipeptide tyrosylglutamate. The newly induced binding sites appear to be identical with pre-existing Cl--dependent binding sites by several criteria: They have a similar pharmacological profile, they are sensitive to low concentrations of Na+, and the number of sites can be further increased by transient exposure to micromolar calcium concentrations. Moreover, binding of [3H]APB, a ligand selective for the Cl--dependent glutamate binding sites, is also increased after glutamate preincubation. The induction of binding sites by high glutamate concentrations, described herein, is calcium-independent, not inhibited by leupeptin and, therefore, different from the previously described activation of binding sites by a calcium-sensitive protease. The high concentration of ligand needed to induce increased binding suggests the presence in hippocampal membranes of a binding site with low, millimolar affinity that is functionally related to the known high-affinity binding sites. Several interpretations of the observed effects and their implications for the possible relationship between the binding site and the synaptic receptor are discussed.
将离体膜或海马切片预先暴露于高浓度（0.1 - 10 mM）的L - 谷氨酸或对此结合位点具有高亲和力的谷氨酸类似物（如quisqualate、同型半胱氨酸盐或氨基己二酸）后，大鼠海马膜中不依赖Na⁺、依赖Cl⁻的谷氨酸结合位点数量增加了两到四倍。N - 甲基天冬氨酸和海人酸无效。短暂暴露于二肽酪氨酰谷氨酸也会诱导类似的结合增加。通过几个标准来看，新诱导的结合位点似乎与预先存在的依赖Cl⁻的结合位点相同：它们具有相似的药理学特征，对低浓度的Na⁺敏感，并且通过短暂暴露于微摩尔浓度的钙，位点数量可以进一步增加。此外，在谷氨酸预孵育后，对依赖Cl⁻的谷氨酸结合位点具有选择性的配体[³H]APB的结合也增加。本文所述的高谷氨酸浓度诱导结合位点的过程不依赖钙，不受亮抑蛋白酶肽抑制，因此不同于先前描述的由钙敏感蛋白酶激活结合位点的情况。诱导结合增加所需的高浓度配体表明海马膜中存在一个具有低毫摩尔亲和力的结合位点，其在功能上与已知的高亲和力结合位点相关。讨论了对观察到的效应的几种解释及其对结合位点与突触受体之间可能关系的影响。
