Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.
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DOI：
10.1371/journal.pone.0042959
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Birnir B
中科院分区：
文献类型：
--
作者：
Mendu SK;Bhandage A;Jin Z;Birnir B
γ-氨基丁酸（GABA）是脑中最重要的神经抑制性递质，它激活位于突触和突触外的神经元GABA-A受体（GABA-A通道）。GABA-A受体是许多临床有用药物的主要靶点。近年来，GABA已被证明是一种免疫调节分子。我们已经在人、小鼠和大鼠的CD 4+和CD 8 + T细胞中检测了GABA-A通道的亚基亚型的表达。通道生理学和药物特异性由GABA-A受体亚型决定，而GABA-A受体亚型又由形成通道的亚基同种型决定。在人、小鼠和大鼠的CD 4+和CD 8 + T细胞中分别鉴定出5、8和13种不同的GABA-A亚基同种型。重要的是，对GABA-A受体施加苯二氮卓敏感性的γ2亚基仅在小鼠T细胞中检测到。免疫印迹和免疫细胞化学显示，丰富的GABA-A通道蛋白的T细胞从所有三个物种。记录GABA激活的全细胞瞬时电流和强直电流。GABA-A通道拮抗剂印防己毒素、SR95531和荷包牡丹碱可抑制该电流。显然，在人类和啮齿类动物的T细胞中，功能性GABA-A通道都有表达，但亚型各不相同。在选择合适的动物模型研究GABA-A通道在CD 4+和CD 8 + T细胞中的生理作用和药理学特性时，以及在选择旨在调节人类T细胞功能的药物时，牢记种间差异是重要的。
γ-aminobutyric acid (GABA) is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronal GABA-A receptors (GABA-A channels) located at synapses and outside of synapses. The GABA-A receptors are primary targets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. We have examined in human, mouse and rat CD4+ and CD8+ T cells which subunit isoforms of the GABA-A channels are expressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn is determined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoforms identified in human, mouse and rat CD4+ and CD8+ T cells, respectively. Importantly, the γ2 subunit that imposes benzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots and immunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activated whole-cell transient and tonic currents were recorded. The currents were inhibited by picrotoxin, SR95531 and bicuculline, antagonists of GABA-A channels. Clearly, in both humans and rodents T cells, functional GABA-A channels are expressed but the subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal models to study the physiological role and pharmacological properties of GABA-A channels in CD4+ and CD8+ T cells and when selecting drugs aimed at modulating the human T cells function.
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影响因子：
16.2
作者：
DRAGUHN, A;VERDORN, TA;SAKMANN, B
通讯作者：
SAKMANN, B
影响因子：
3.4
作者：
Alakuijala, A;TalviOja, K;Pasternack, M
通讯作者：
Pasternack, M
影响因子：
5.3
作者：
Jin Z;Bazov I;Kononenko O;Korpi ER;Bakalkin G;Birnir B
通讯作者：
Birnir B
影响因子：
3.8
作者：
GERBER, JC;HARE, TA
通讯作者：
HARE, TA
DOI：
10.1073/pnas.0915139107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Bhat, Roopa;Axtell, Robert;Steinman, Lawrence
通讯作者：
Steinman, Lawrence