THE EFFECTS OF A SERIES OF OMEGA-PHOSPHONIC ALPHA-CARBOXYLIC AMINO-ACIDS ON ELECTRICALLY EVOKED AND EXCITANT AMINO ACID-INDUCED RESPONSES IN ISOLATED SPINAL-CORD PREPARATIONS
THE EFFECTS OF A SERIES OF OMEGA-PHOSPHONIC ALPHA-CARBOXYLIC AMINO-ACIDS ON ELECTRICALLY EVOKED AND EXCITANT AMINO ACID-INDUCED RESPONSES IN ISOLATED SPINAL-CORD PREPARATIONS
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DOI：
10.1111/j.1476-5381.1982.tb08758.x
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发表时间：
1982-01-01
影响因子：
7.3
通讯作者：
WATKINS, JC
中科院分区：
文献类型：
--
作者：
EVANS, RH;FRANCIS, AA;WATKINS, JC
1在青蛙或未成熟大鼠的离体脊髓制备物中研究了一系列ω-膦酸α-羧酸氨基酸对诱发电活动的抑制作用和兴奋性氨基酸拮抗剂特性。2当对背根诱发腹根电位进行测试时，从2-氨基-5-膦酰基戊酸到2-氨基-8-膦酰基辛酸的同源系列的成员显示出与这些物质选择性拮抗N-甲基-d-谷氨酸诱导的运动神经元去极化的能力。32-氨基-5-膦酰基戊酸是该系列中最有效的物质，其拮抗N-甲基-d-谷氨酸反应的表观KD为1.4 μ m。4（+）-和（-）- 形式的2-氨基-5-膦酰基戊酸盐表明，N-甲基-d-天冬氨酸拮抗剂活性和神经元抑制作用的这种物质，2-氨基-4-膦酰基丁酸的（-）-和（+）-形式具有不同的作用。该物质的（-）-形式对N-甲基-d-天冬氨酸盐、使君子酸盐和红藻氨酸盐诱导的去极化具有相对较弱的非选择性拮抗作用，并且当对诱发电活动进行测试时，具有类似的弱拮抗作用。（+）-形式在抑制电诱发活动方面比（-）-形式更有效，但不拮抗对氨基酸兴奋剂的反应。当浓度高于抑制电诱发活动所需的浓度时，（+）-型产生去极化。该作用被2-氨基-5-膦酰基戊酸阻断。
1The depressant actions on evoked electrical activity and the excitant amino acid antagonist properties of a range of ω‐phosphonic α‐carboxylic amino acids have been investigated in the isolated spinal cord preparations of the frog or immature rat.2When tested on dorsal root‐evoked ventral root potentials, members of the homologous series from 2‐amino‐5‐phosphonovaleric acid to 2‐amino‐8‐phosphonooctanoic acid showed depressant actions which correlated with the ability of the substances to antagonize selectively motoneuronal depolarizations induced by N‐methyl‐d‐aspartate.32‐Amino‐5‐phosphonovalerate was the most potent substance of the series giving an apparentKDof 1.4 μmfor the antagonism of responses to N‐methyl‐d‐aspartate.4A comparison of the (+)‐ and (—)‐forms of 2‐amino‐5‐phosphonovalerate indicated that the N‐methyl‐d‐aspartate antagonist activity and the neuronal depressant action of this substance were both due mainly to the (—)‐isomer.5The (—)‐ and (+)‐forms of 2‐amino‐4‐phosphonobutyrate had different actions. The (—)‐form of this substance had a relatively weak and non‐selective antagonist action on depolarizations induced by N‐methyl‐d‐aspartate, quisqualate and kainate and a similarly weak depressant effect when tested on evoked electrical activity. The (+)‐form was more potent than the (—)‐form in depressing electrically evoked activity but did not antagonize responses to amino acid excitants. At concentrations higher than those required to depress electrically evoked activity, the (+)‐form produced depolarization. This action was blocked by 2‐amino‐5‐phosphonovalerate.