A novel domain of the inhibitory glycine receptor determining antagonist efficacies: further evidence for partial agonism resulting from self-inhibition.
A novel domain of the inhibitory glycine receptor determining antagonist efficacies: further evidence for partial agonism resulting from self-inhibition.
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决定拮抗剂功效的抑制性甘氨酸受体的新结构域：自我抑制导致部分激动的进一步证据。
DOI：
10.1124/mol.56.3.464
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发表时间：
1999
影响因子：
3.6
通讯作者：
H. Betz
中科院分区：
文献类型：
--
作者：
V. Schmieden;J. Kuhse;H. Betz
抑制性甘氨酸受体（GlyR）的N-末端胞外区中的不同氨基侧链已被证明对于配体识别至关重要。在这里，我们描述了一个新的域的GlyRalpha 1亚基，构成了一个重要的决定因素的拮抗剂活性。拮抗剂士的宁，nipecoic酸，异丁酸显示降低效力的重组GlyR形成的α 1亚基，其中赖氨酸104，苯丙氨酸108，或苏氨酸112被丙氨酸取代。相反，激动剂亲和力在这些突变受体略有增加。牛磺酸和β-氨基异丁酸，这是在野生型GlyR的部分激动剂，表现为完全激动剂的突变体GlyR和未能抑制甘氨酸诱导的电流。这与alpha 1亚基104、108和112位的非极性残基降低β-氨基酸的拮抗性结合而非激动性结合一致。我们的数据支持一种模型，其中β-氨基酸的部分激动作用来自其自抑制活性。
Different amino side chains in the N-terminal extracellular region of the inhibitory glycine receptor (GlyR) have been shown to be crucial for ligand recognition. Here we describe a novel domain of the GlyRalpha1 subunit that constitutes an important determinant of antagonist activity. The antagonists strychnine, nipecotic acid, and isobutyric acid displayed reduced potencies at recombinant GlyRs formed from alpha1 subunits, in which lysine 104, phenylalanine 108, or threonine 112 were replaced by alanine. Agonist affinities, in contrast, were slightly increased at these mutant receptors. Taurine and beta-aminoisobutyric acid, which are partial agonists at the wild-type GlyR, behaved as full agonists at the mutant GlyRs and failed to inhibit glycine-induced currents. This is consistent with apolar residues at positions 104, 108, and 112 of the alpha1 subunit reducing the antagonistic, but not the agonistic, binding of beta-amino acids. Our data support a model in which the partial agonism of beta-amino acids results from their self-inhibitory activity.
大鼠脑和脊髓中甘氨酸受体及其信使 RNA 的异质性。
DOI：
10.1126/science.2845580
发表时间：
1988
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Akagi,H;Miledi,R
通讯作者：
Miledi,R