Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells
作者机构：State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceFudan UniversityShanghai 200032.China
出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)
年 卷 期：2022年第38卷第6期
页 面：622-636页
核心收录：
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(81790640.32070989.31872766.31571075.82070993.and 31571072) the Ministry of Science and Technology of China(201 ICB504602 and 2015AA020512) Shanghai Municipal Science and Technology Major Project(2018SHZDZX01) ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,and Sanming Project of Medicine in Shenzhen(SZSM202011015).
主 题：Glucagon-like peptide-1 Exendin-4 GABA current Retinal ganglion cells Neuromodulation
摘 要：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-aminobutyric acid receptor(GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells(GCs).Pre-incubation with the stimulatory G protein(G,)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 RpcAMP/KT-5720.The_exendin-4 effect was accompanied by an increase in[Ca2+];of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution.Furthermore,when the activity of calmodulin(CaM)and CaMdependent 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 G,/cAMP-PKA/IPs/Ca+/CaM/CaMKIl signaling pathway,following the activation of GLP-1Rs.
维普期刊数据库