Chen Chao-Yin, Ling Eh Erh-hsin, Horowitz John M, Bonham Ann C
Division of Cardiovascular Medicine, University of California, Davis, CA 95616, USA.
J Physiol. 2002 Feb 1;538(Pt 3):773-86. doi: 10.1113/jphysiol.2001.012948.
Presynaptic metabotropic glutamate receptors (mGluRs) serve as autoreceptors throughout the CNS to inhibit glutamate release and depress glutamatergic transmission. Both presynaptic and postsynaptic mGluRs have been implicated in shaping autonomic signal transmission in the nucleus tractus solitarius (NTS). We sought to test the hypothesis that activation of presynaptic mGluRs depresses neurotransmission between primary autonomic afferent fibres and second-order NTS neurones. In second-order NTS neurones, excitatory postsynaptic currents (EPSCs) synaptically evoked by stimulation of primary sensory afferent fibres in the tractus solitarius (ts) and currents postsynaptically evoked by alpha-amino-3-hydroxy-4-isoxazoleproprionic acid (AMPA) were studied in the presence and absence of mGluR agonists and antagonists. Real-time quantitative RT-PCR (reverse transcription-polymerase chain reaction) was used to determine whether the genes for the mGluR subtypes were expressed in the cell bodies of the primary autonomic afferent fibres. Agonist activation of Group II and III but not Group I mGluRs reduced the peak amplitude of synaptically (ts) evoked EPSCs in a concentration-dependent manner while having no effect on postsynaptically (AMPA) evoked currents recorded in the same neurones. At the highest concentrations, the Group II agonist, (2S,3S,4S)-CCG/(2S,1'S,2'S)-2-carboxycyclopropyl (L-CCG-I), decreased the amplitude of the ts-evoked EPSCs by 39 % with an EC50 of 21 microM, and the Group III agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), decreased the evoked EPSCs by 71 % with an EC50 of 1 mM. mRNA for all eight mGluR subtypes was detected in the autonomic afferent fibre cell bodies in the nodose and jugular ganglia. Group II and III antagonists ((2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG) and (RS)-alpha-methylserine-O-phosphate (MSOP)), at concentrations that blocked the respective agonist-induced synaptic depression, attenuated the frequency-dependent synaptic depression associated with increasing frequencies of ts stimulation by 13-34 % and 13-19 %, respectively (P < 0.05, for each). We conclude that Group II and III mGluRs (synthesized in the cell bodies of the primary autonomic afferent fibres and transported to the central terminals in the NTS) contribute to the depression of autonomic signal transmission by attenuating presynaptic release of glutamate.
突触前代谢型谷氨酸受体（mGluRs）在整个中枢神经系统中作为自身受体发挥作用，抑制谷氨酸释放并降低谷氨酸能传递。突触前和突触后的mGluRs均参与孤束核（NTS）中自主神经信号传递的形成。我们试图验证以下假设：突触前mGluRs的激活会抑制初级自主传入纤维与NTS二级神经元之间的神经传递。在NTS二级神经元中，研究了在存在和不存在mGluR激动剂及拮抗剂的情况下，刺激孤束（ts）中的初级感觉传入纤维突触诱发的兴奋性突触后电流（EPSCs）以及α-氨基-3-羟基-4-异恶唑丙酸（AMPA）突触后诱发的电流。采用实时定量逆转录聚合酶链反应（RT-PCR）来确定mGluR亚型的基因是否在初级自主传入纤维的细胞体中表达。II组和III组而非I组mGluRs的激动剂激活以浓度依赖性方式降低了突触（ts）诱发的EPSCs的峰值幅度，而对同一神经元中突触后（AMPA）诱发的电流没有影响。在最高浓度下，II组激动剂（2S,3S,4S）-CCG/（2S,1'S,2'S）-2-羧基环丙基（L-CCG-I）使ts诱发的EPSCs幅度降低了39%，EC50为21μM，III组激动剂L（+）-2-氨基-4-膦酸丁酸（L-AP4）使诱发的EPSCs降低了71%，EC50为1 mM。在结状神经节和颈静脉神经节的自主传入纤维细胞体中检测到了所有8种mGluR亚型的mRNA。II组和III组拮抗剂（（2S,3S,4S）-2-甲基-2-（羧基环丙基）甘氨酸（MCCG）和（RS）-α-甲基丝氨酸-O-磷酸（MSOP））在阻断各自激动剂诱导的突触抑制的浓度下，分别使与ts刺激频率增加相关的频率依赖性突触抑制减弱了13% - 34%和13% - 19%（每组P < 0.05）。我们得出结论，II组和III组mGluRs（在初级自主传入纤维的细胞体中合成并转运至NTS的中枢终末）通过减弱谷氨酸的突触前释放来促进自主神经信号传递的抑制。
