Lynch Joseph W
Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, Brisbane QLD 4072, Australia.
Neuropharmacology. 2009 Jan;56(1):303-9. doi: 10.1016/j.neuropharm.2008.07.034. Epub 2008 Aug 3.
The glycine receptor chloride channel (GlyR), a member of the pentameric Cys-loop ion channel receptor family, mediates inhibitory neurotransmission in the spinal cord, brainstem and retina. They are also found presynaptically, where they modulate neurotransmitter release. Functional GlyRs are formed from a total of five subunits (alpha1-alpha4, beta). Although alpha subunits efficiently form homomeric GlyRs in recombinant expression systems, homomeric alpha1, alpha3 and alpha4 GlyRs are weakly expressed in adult neurons. In contrast, alpha2 homomeric GlyRs are abundantly expressed in embryonic neurons, although their numbers decline sharply by adulthood. Numerous lines of biochemical, biophysical, pharmacological and genetic evidence suggest the majority of glycinergic neurotransmission in adults is mediated by heteromeric alpha1beta GlyRs. Immunocytochemical co-localisation experiments suggest the presence of alpha2beta, alpha3beta and alpha4beta GlyRs at synapses in the adult mouse retina. Immunocytochemical and electrophysiological evidence also implicates alpha3beta GlyRs as important mediators of glycinergic inhibitory neurotransmission in nociceptive sensory neuronal circuits in peripheral laminae of the spinal cord dorsal horn. It is yet to be determined why multiple GlyR synaptic subtypes are differentially distributed in these and possibly other locations. The development of pharmacological agents that can discriminate strongly between different beta subunit-containing GlyR isoforms will help to address this issue, and thereby provide important insights into a variety of central nervous system functions including retinal signal processing and spinal pain mechanisms. Finally, agents that selectively potentiate different GlyR isoforms may be useful as therapeutic lead compounds for peripheral inflammatory pain and movement disorders such as spasticity.
甘氨酸受体氯离子通道（GlyR）是五聚体半胱氨酸环离子通道受体家族的成员，介导脊髓、脑干和视网膜中的抑制性神经传递。它们也存在于突触前，在那里调节神经递质的释放。功能性GlyR由总共五个亚基（α1-α4，β）组成。虽然α亚基在重组表达系统中能有效地形成同聚体GlyR，但同聚体α1、α3和α4 GlyR在成年神经元中表达较弱。相比之下，α2同聚体GlyR在胚胎神经元中大量表达，尽管其数量在成年后急剧下降。大量的生化、生物物理、药理学和遗传学证据表明，成年人中大多数甘氨酸能神经传递是由异聚体α1β GlyR介导的。免疫细胞化学共定位实验表明，成年小鼠视网膜突触中存在α2β、α3β和α4β GlyR。免疫细胞化学和电生理证据也表明，α3β GlyR是脊髓背角外周层伤害性感觉神经元回路中甘氨酸能抑制性神经传递的重要介质。尚不清楚为什么多种GlyR突触亚型在这些以及可能其他位置存在差异分布。能够强烈区分不同含β亚基的GlyR亚型的药理学试剂的开发将有助于解决这个问题，从而为包括视网膜信号处理和脊髓疼痛机制在内的各种中枢神经系统功能提供重要见解。最后，选择性增强不同GlyR亚型的试剂可能作为外周炎性疼痛和运动障碍（如痉挛）的治疗先导化合物有用。
