1-氨基环丙烷羧酸对大鼠海马突触体中N-甲基-D-天冬氨酸刺激的[3H]-去甲肾上腺素释放的影响。
Effect of 1-aminocyclopropanecarboxylic acid on N-methyl-D-aspartate-stimulated [3H]-noradrenaline release in rat hippocampal synaptosomes.
作者信息
Clos M V, Garcia Sanz A, Trullas R, Badia A
机构信息
Department de Farmacologia i Psiquiatria, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
出版信息
Br J Pharmacol. 1996 Jun;118(4):901-4. doi: 10.1111/j.1476-5381.1996.tb15484.x.
Abstract
- The effect of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor complex that exhibits neuroprotective, anxiolytic and antidepressant-like actions, was investigated in a functional assay for presynaptic NMDA receptors. 2. NMDA (100 microM) produced a 36% increase of tritium efflux above basal efflux in rat hippocampal synaptosomes preincubated with [3H]-noradrenaline ([3H]-NA), reflecting a release of tritiated noradrenaline. This effect was prevented by 10 microM 7-chlorokynurenic acid, an antagonist of the glycine site of the NMDA receptor. 3. Glycine enhanced the effect of NMDA with Emax and EC50 values of 84 +/- 11% and 1.82 +/- 0.04 microM, respectively. ACPC potentiated the effect of NMDA on tritium overflow with a lower EC50 (43 +/- 6 nM) and a lower maximal effect (Emax = 40 +/- 9%) than glycine. Furthermore, ACPC (0.1 microM) shifted the EC50 of glycine from 1.82 microM to > or = 3 mM. 4. These results show that ACPC can reduce the potentiation by glycine of NMDA-evoked [3H]-NA release and hence, may act as an antagonist at the glycine site of presynaptic hippocampal NMDA receptors when the concentration of glycine is high.
摘要
- 1-氨基环丙烷羧酸（ACPC）是N-甲基-D-天冬氨酸（NMDA）受体复合物甘氨酸位点的部分激动剂，具有神经保护、抗焦虑和抗抑郁样作用。本研究在突触前NMDA受体的功能测定中对其作用进行了研究。2. NMDA（100微摩尔）使预先用[3H]-去甲肾上腺素（[3H]-NA）预孵育的大鼠海马突触体中的氚流出量比基础流出量增加36%，这反映了氚化去甲肾上腺素的释放。NMDA受体甘氨酸位点的拮抗剂10微摩尔7-氯犬尿氨酸可阻止这种作用。3. 甘氨酸增强了NMDA的作用，其最大效应（Emax）和半数有效浓度（EC₅₀）分别为84±11%和1.82±0.04微摩尔。与甘氨酸相比，ACPC增强NMDA对氚溢出的作用时，其EC₅₀较低（43±6纳摩尔），最大效应也较低（Emax = 40±9%）。此外，ACPC（0.1微摩尔）将甘氨酸的EC₅₀从1.82微摩尔转变为≥3毫摩尔。4. 这些结果表明，当甘氨酸浓度较高时，ACPC可降低甘氨酸对NMDA诱发的[3H]-NA释放的增强作用，并因此可能作为突触前海马NMDA受体甘氨酸位点的拮抗剂发挥作用。
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