Rat brain synaptosomal membranes that are depleted of endogenous excitatory amino acids cannot bind [(+)-5-methyl-10, 11-dihydro-5H-dibenzo(a,d]cyclohept-5,10-imine maleate] ([3H]MK-801). However, they do so upon the restoration of excitatory amino acid agonists such as L-glutamate. [3H]MK-801 provides a molecular probe which is specific for a binding site located within the ionophore of the N-methyl-D-aspartate-type excitatory amino acid receptor, [3H]MK-801 does not bind to non-N-methyl-D-aspartate excitatory amino acid receptors. Exploiting [3H]MK-801 binding as a quantitative measure of agonist activity with respect to ability of inducing the open channel conformation, the present study demonstrates that L-homocysteate is an agonist almost equivalent to L-glutamate in terms of efficacy (maximal N-methyl-D-aspartate response) as well as potency (EC50). The effect of L-homocysteate was dose-dependent, stereospecific (L-homocysteate greater than DL-homocysteate greater than D-homocysteate), suppressible by the N-methyl-D-aspartate-selective competitive antagonist (+/-)-3(2-carboxy-piperazine-4-yl)propyl-l-phosphonate, and potentiated by the N-methyl-D-aspartate-selective "allosteric" modulator glycine. The demonstrated inactivity of L-homocysteine (and virtually all naturally occurring, non-acidic amino acids) implies that the omega-sulphonic acid moiety is an acceptable substitute for the omega carboxyl group for activating the N-methyl-D-aspartate receptor. While the potency of L-homocysteate at N-methyl-D-aspartate receptors was by a factor of only 1.6 smaller than that of L-glutamate, the affinity of L-homocysteate for kainate-type excitatory amino acid receptors was approximately four-fold lower than that of L-glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

译文

消耗内源性兴奋性氨基酸的大鼠脑突触体膜不能结合 [(+)-5-甲基-10,11-dihydro-5H-dibenzo(a,d]cyclohept-5,马来酸10-亚胺] ([3H]MK-801)。它们是在兴奋性氨基酸激动剂如L-谷氨酸恢复时这样做的。[3H]MK-801提供了一种分子探针,该探针对位于N-甲基-D-天冬氨酸型兴奋性氨基酸受体的离子载体内的结合位点具有特异性,[3H]MK-801不结合非N-甲基-D-天冬氨酸兴奋性氨基酸受体。利用 [3H]MK-801结合作为关于诱导开放通道构象能力的激动剂活性的定量测量,本研究表明,L-同型半胱氨酸在功效 (最大N-甲基-D-天冬氨酸反应) 和效力 (EC50) 方面几乎等同于L-谷氨酸。L-同型半胱氨酸的作用是剂量依赖性的,立体特异性 (L-高半胱氨酸大于DL-高半胱氨酸大于D-高半胱氨酸),可被N-甲基-D-天冬氨酸选择性竞争性拮抗剂 (/-)-3(2-羧基哌嗪-4-基) 丙基-l-膦酸酯抑制,并由N-甲基-D-天冬氨酸选择性 “变构” 调节剂甘氨酸增强。已证明L-高半胱氨酸 (几乎所有天然存在的,非酸性氨基酸) 意味着 ω-磺酸部分是激活N-甲基-D-天冬氨酸受体的 ω 羧基的可接受替代品。而L-同型半胱氨酸在N-甲基-D-天冬氨酸受体上的效力仅比1.6小L-谷氨酸,L-同型半胱氨酸对红藻氨酸型兴奋性氨基酸受体的亲和力大约比L-谷氨酸低4倍。(摘要截短于250字)

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