Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes.
Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes.
复制标题
重组α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体亚型的复杂药理学特性。
作者：
E. Stein;J. Cox;P. Seeburg;T. Verdoorn
使用两电极电压钳在注射 RNA 的非洲爪蟾卵母细胞中检查了两种谷氨酸受体亚型 GluR-A/B 和 GluR-B/D 的药理学特性。浓度-反应关系显示，L-谷氨酸、红藻氨酸和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯 (AMPA) 的效力在两种受体亚型之间略有不同，但激动剂效力的顺序没有变化。 GluR-A/B 受体的 EC50 值对于 AMPA 为 3.31 microM，对于谷氨酸为 6.16 microM，对于红藻氨酸为 57.5 microM，而对于 GluR-B/D 受体的 EC50 值对于 AMPA、L-谷氨酸和红藻氨酸分别为 5.01 microM、32.3 microM 和 64.6 microM。通过 Schild 分析对 6-氰基-7-硝基喹喔啉-2,3-二酮 (CNQX) 和 2,3-二羟基-6-硝基-7-氨磺酰基-苯并(f)喹喔啉 (NBQX) 的效力进行定量。 NBQX 阻断 GluR-A/B 受体介导的电流的效力根据用于激活受体的激动剂而变化（pA2 值如下：红藻氨酸阻断，7.23 +/- 0.01；L-谷氨酸，6.78 +/- 0.02；AMPA，6.95 +/- 0.02）。在表达 GluR-B/D 受体的细胞中，激动剂之间的差异不太明显（pA2 值：红藻氨酸，7.28 +/- 0.01；L-谷氨酸，7.30 +/- 0.02；AMPA，7.35 +/- 0.01）。在每种情况下，Schild 回归的斜率与统一没有不同，这与 NBQX 对这些受体的竞争性拮抗作用一致。 CNQX 还竞争性阻断 GluR-A/B 和 GluR-B/D 受体，但不如 NBQX 有效，并且不区分激动剂或亚基组合。这些数据表明，L-谷氨酸、红藻氨酸和 AMPA 与重组 AMPA 受体上的不同受体亚结构结合，并且 NBQX 而不是 CNQX 以不同的亲和力与这些位点结合。此外，由于这些结合位点的特性在 GluR-A/B 和 GluR-B/D 受体之间有所不同，我们的研究结果为旨在识别参与激动剂和拮抗剂结合的受体结构域的突变分析提供了基础。
The pharmacological properties of two glutamate receptor subtypes, GluR-A/B and GluR-B/D, were examined in RNA-injected Xenopus oocytes using two-electrode voltage clamp. Concentration-response relations revealed that the potencies of L-glutamate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) varied slightly between the two receptor subtypes, but the rank order of agonist potency did not. The EC50 values for GluR-A/B receptors were 3.31 microM for AMPA, 6.16 microM for glutamate, and 57.5 microM for kainate, whereas the EC50 values for GluR-B/D receptors were 5.01 microM, 32.3 microM, and 64.6 microM for AMPA, L-glutamate, and kainate, respectively. The potencies of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) were quantified by Schild analysis. The potency of NBQX at blocking currents mediated by GluR-A/B receptors changed depending on the agonist used to activate the receptors (pA2 values were as follows: for block of kainate, 7.23 +/- 0.01; L-glutamate, 6.78 +/- 0.02; AMPA, 6.95 +/- 0.02). Differences between agonists were less marked in cells expressing GluR-B/D receptors (pA2 values: kainate, 7.28 +/- 0.01; L-glutamate, 7.30 +/- 0.02; AMPA, 7.35 +/- 0.01). In each case, the slope of the Schild regression was not different from unity, consistent with competitive antagonism of these receptors by NBQX. CNQX also blocked GluR-A/B and GluR-B/D receptors competitively but was less potent than NBQX and did not differentiate between agonists or subunit combination. These data suggest that L-glutamate, kainate, and AMPA bind to different receptor substructures on recombinant AMPA receptors and that NBQX but not CNQX binds to these sites with different affinities. Moreover, because the properties of these binding sites vary between GluR-A/B and GluR-B/D receptors, our findings provide a basis for mutational analysis aimed at identifying receptor domains involved in agonist and antagonist binding.
非洲爪蟾卵母细胞中表达的同源 GluR1 兴奋性氨基酸受体。
影响因子：
3.6
作者：
Dawson,TL;Nicholas,RA;Dingledine,R
通讯作者：
Dingledine,R
影响因子：
3.6
作者：
T. Verdoorn;N. W. Kleckner;R. Dingledine
通讯作者：
T. Verdoorn;N. W. Kleckner;R. Dingledine