Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells.
Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells.
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GABA受体GLP-1和exendin-4调节大鼠视网膜神经节细胞的信号机制
DOI：
10.1007/s12264-022-00826-9
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发表时间：
2022-06
影响因子：
5.6
通讯作者：
Zhong, Yong-Mei
中科院分区：
文献类型：
--
作者：
Zhang, Tao;Ruan, Hang-Ze;Wang, Yong-Chen;Shao, Yu-Qi;Zhou, Wei;Weng, Shi-Jun;Zhong, Yong-Mei
胰高血糖素样肽-1 (GLP-1) 在视网膜神经元中表达，但其在视网膜中的作用很大程度上未知。在这里，我们证明 GLP-1 或 GLP-1 受体（GLP-1R；一种 G 蛋白偶联受体）激动剂 exendin-4 通过分离的大鼠视网膜神经节细胞（GC）中的 GLP-1R 抑制 γ-氨基丁酸受体（GABAR）介导的电流。与刺激性 G 蛋白 (Gs) 抑制剂 NF 449 预孵育消除了 exendin-4 效应。 exendin-4 诱导的抑制可通过灌注 8-Br-cAMP（cAMP 类似物）来模拟，但可被蛋白激酶 A (PKA) 抑制剂 Rp-cAMP/KT-5720 消除。 Exendin-4 效应伴随着通过 IP3 敏感途径的 GC 中 [Ca2+]i 的增加，并且在无 Ca2+ 溶液中被阻断。此外，当钙调蛋白 (CaM) 和 CaM 依赖性蛋白激酶 II (CaMKII) 的活性受到抑制时，exendin-4 的作用就会被消除。与此一致的是，exendin-4 抑制大鼠视网膜切片中 GC 中 GABAR 介导的光诱发抑制性突触后电流。这些结果表明，在 GLP-1R 激活后，exendin-4 诱导的抑制可能是由不同的 Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII 信号通路介导的。本文的在线版本 (10.1007/s12264-022-00826-9) 包含补充材料，可供授权用户使用。
Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs. The online version of this article (10.1007/s12264-022-00826-9) contains supplementary material, which is available to authorized users.
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影响因子：
2.5
作者：
Fischer, Andy J.;Stanke, Jennifer J.;Omar, Ghezal
通讯作者：
Omar, Ghezal
影响因子：
4.5
作者：
Aguayo, LG;Espinoza, F;Satin, LS
通讯作者：
Satin, LS
影响因子：
3.3
作者：
Chen, L.;Yang, X. -L.
通讯作者：
Yang, X. -L.
DOI：
10.1016/s0167-4838(00)00270-3
发表时间：
2001-03-09
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY
影响因子：
--
作者：
Hällbrink, M;Holmqvist, T;Langel, Ü
通讯作者：
Langel, Ü
影响因子：
8.1
作者：
Cork SC;Richards JE;Holt MK;Gribble FM;Reimann F;Trapp S
通讯作者：
Trapp S