Activation of human α1 and α2 homomeric glycine receptors by taurine and GABA
Activation of human α1 and α2 homomeric glycine receptors by taurine and GABA
复制标题
牛磺酸和 GABA 激活人类 α1 和 α2 同聚甘氨酸受体
DOI：
10.1111/j.1469-7793.2001.t01-1-00741.x
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
P. Bregestovski
中科院分区：
文献类型：
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作者：
D. Jan;B. David;H. Korn;P. Bregestovski
1 人 (H) 甘氨酸受体 (GlyR) 的两个配体结合 α 亚基 α1 和 α2 分别参与成人和新生儿脊髓的抑制性突触。在爪蟾卵母细胞或人胚肾 HEK-293 细胞系中研究了同聚 αH1 和 αH2 GlyR 被甘氨酸、牛磺酸和 GABA 激活的能力。 2 在 HEK 细胞的外侧斑块中，甘氨酸、牛磺酸和 GABA 以相同的主要单一电导激活两个 GlyR，即 αH1 为 85 ± 3 pS (n= 6)，αH2 为 95 ± 5 pS (n = 4)。 3 αH1 和 αH2 GlyR 对甘氨酸的敏感性差异很大。在非洲爪蟾卵母细胞中，αH1 (n= 44) 的甘氨酸 EC50 (EC50gly) 介于 25 至 280 μm 之间，αH2 (n= 52) 的 EC50 介于 46 至 541 μm 之间。对于这两种受体，在最大甘氨酸反应较低的细胞上发现了最高的 EC50gly 值。 4 牛磺酸和GABA的作用取决于EC50gly：（i）它们的EC50值与EC50gly线性相关，EC50tau≈10 EC50gly，EC50GABA≈500-800 EC50gly； (ii) 它们可以作为完全激动剂或弱激动剂，具体取决于 EC50gly。 5 无论 EC50gly 为何，甘氨酸的 Hill 系数 (nH) 均保持稳定，而牛磺酸的 Hill 系数 (nH) 随着 EC50tau 的增加而降低。 6 通过在非洲爪蟾卵母细胞的外侧斑块上快速应用饱和浓度的激动剂来评估，两个 GlyR 上的甘氨酸和牛磺酸的脱敏程度相似，且不超过 50%。 7 我们关于 EC50gly 变化以及牛磺酸和 GABA 随后行为的数据可以通过简单的 del Castillo-Katz 方案定性描述，假设激动剂门控常数变化而结合常数稳定。然而，该模型无法解释甘氨酸 Hill 系数的稳定性，这表明 EC50 的调节涉及其他机制。
1 Two ligand binding α subunits, α1 and α2, of the human (H) glycine receptor (GlyR) are involved at inhibitory synapses in the adult and neonatal spinal cord, respectively. The ability of homomeric αH1 and αH2 GlyRs to be activated by glycine, taurine and GABA was studied in Xenopus oocytes or in the human embryonic kidney HEK‐293 cell line. 2 In outside‐out patches from HEK cells, glycine, taurine and GABA activated both GlyRs with the same main unitary conductance, i.e. 85 ± 3 pS (n= 6) for αH1, and 95 ± 5 pS (n = 4) for αH2. 3 The sensitivity of both αH1 and αH2 GlyRs to glycine was highly variable. In Xenopus oocytes the EC50 for glycine (EC50gly) was between 25 and 280 μm for αH1 (n= 44) and between 46 and 541 μm for αH2 (n= 52). For both receptors, the highest EC50gly values were found on cells with low maximal glycine responses. 4 The actions of taurine and GABA were dependent on the EC50gly: (i) their EC50 values were linearly correlated to EC50gly, with EC50tau≈ 10 EC50gly and EC50GABA≈ 500‐800 EC50gly; (ii) they could act either as full or weak agonists depending on the EC50gly. 5 The Hill coefficient (nH) of glycine remained stable regardless of the EC50gly whereas nH for taurine decreased with increasing EC50tau. 6 The degree of desensitization, evaluated by fast application of saturating concentrations of agonist on outside‐out patches from Xenopus oocytes, was similar for glycine and taurine on both GlyRs and did not exceed 50 %. 7 Our data concerning the variations of EC50gly and the subsequent behaviour of taurine and GABA could be qualitatively described by the simple del Castillo‐Katz scheme, assuming that the agonist gating constant varies whereas the binding constants are stable. However, the stability of the Hill coefficient for glycine was not explained by this model, suggesting that other mechanisms are involved in the modulation of EC50.