Mizzi Nicole, Blundell Renald
Department of Physiology and Biochemistry, University of Malta, MSD 2080, Malta.
Department of Physiology and Biochemistry, University of Malta, MSD 2080, Malta; Molecular Centre for Biotechnology and Biobanking, University of Malta, Msida, MSD 2080, Malta.
Mol Aspects Med. 2025 Jun;103:101360. doi: 10.1016/j.mam.2025.101360. Epub 2025 Apr 7.
Glycine receptors are considered as an integral part of higher brain function in mammals. The main function of glycine receptor is fast inhibitory transmission brought about by glycine neurotransmitter, its full agonist. This receptor is part of the glycinergic system which controls key physiological functions such as motor coordination, regulation of the rhythm of respiration and pain signalling. Glycine, a non-essential amino acid, causes hyperpolarisation within the glycine receptor, leading this ion channel to open and allow influx of chloride ion. The glycine receptor is found within the central nervous system and peripheral nervous system. It has also been found within amacrine cells, as well as renal medulla and cortex. The glycine receptor is a pentameric ligand-gated channel, part of the Cys-loop superfamily. It is composed of large ECD, C terminus, transmembrane domain M1-M4, and a 4α:1β glycine receptor subunit stoichiometry. The glycine receptor can be found as either homomeric or heteromeric subtypes. Alpha subtypes are crucial for important physiological functions such as breathing control and nociceptive system processing while the beta subunit aids in glycine receptor clustering and synapse stabilisation with its interaction with gephyrin scaffold protein. When hyperpolarised, the receptor transitions between close, open, and desensitised states. Factors that affect the activity and function of glycine receptors are gephyrin, ivermectin, strychnine and picrotoxin while certain endogenous modulators include partial agonists, positive allosteric modulator, antagonists, and bidirectional modulator are used for pharmacological modulation. Further studies need to be carried out on how glycine receptors are also implicated in chronic pain and nociception, epilepsy, autoimmune diseases and hyperekplexia.
甘氨酸受体被认为是哺乳动物高级脑功能的一个组成部分。甘氨酸受体的主要功能是由其完全激动剂甘氨酸神经递质介导的快速抑制性传递。该受体是甘氨酸能系统的一部分，该系统控制着诸如运动协调、呼吸节律调节和疼痛信号传导等关键生理功能。甘氨酸是一种非必需氨基酸，可在甘氨酸受体内引起超极化，导致该离子通道开放并允许氯离子内流。甘氨酸受体存在于中枢神经系统和周围神经系统中。它也存在于无长突细胞以及肾髓质和皮质中。甘氨酸受体是一种五聚体配体门控通道，属于半胱氨酸环超家族。它由大的细胞外结构域、C末端、跨膜结构域M1 - M4以及4α:1β的甘氨酸受体亚基化学计量组成。甘氨酸受体可以是同聚体或异聚体亚型。α亚型对于诸如呼吸控制和伤害感受系统处理等重要生理功能至关重要，而β亚基通过与桥连蛋白支架蛋白相互作用，有助于甘氨酸受体聚集和突触稳定。当超极化时，受体在关闭、开放和脱敏状态之间转变。影响甘氨酸受体活性和功能的因素有桥连蛋白、伊维菌素、士的宁和印防己毒素，而某些内源性调节剂包括部分激动剂、正变构调节剂、拮抗剂和双向调节剂用于药理学调节。关于甘氨酸受体如何也与慢性疼痛和伤害感受、癫痫、自身免疫性疾病和僵人综合征有关，还需要进一步研究。
