Laboratorio de Neurofarmacología, Centro de Investigaciones Médicas, Facultad de Medicina, Universidad de Talca, Av. Lircay S/N, Talca 3460000, Chile.
Facultad de Educación, Universidad de Las Américas, República 71, Santiago 8370040, Chile.
Curr Vasc Pharmacol. 2022;20(3):221-229. doi: 10.2174/1570161120666220720101352.
Glycine Receptors (GlyRs) are cell-surface transmembrane proteins that belong to the Cysloop ligand-gated ion channels superfamily (Cys-loop LGICs). Functional glycine receptors are conformed only by α-subunits (homomeric channels) or by α- and β-subunits (heteromeric channels). The role of glycine as a cytoprotective is widely studied. New information about glycine modulation of vascular endothelial cells (ECs) function emerged last year. Glycine and its receptors are recognized to play a role as neurovascular protectors by a mechanism that involves α2GlyRs. Interestingly, the expression of α2GlyRs reduces after stroke injury. However, glycine reverses the inhibition of α2GlyRs by a mechanism involving the VEGF/pSTAT3 signaling. On the other hand, consistent evidence has demonstrated that ECs participate actively in the innate and adaptive immunological response. We recently reported that GlyRs are modulated by interleukin-1β, suggesting new perspectives to explain the immune modulation of vascular function in pathological conditions such as cerebrovascular stroke. In this work, we distinguish the role of glycine and the allosteric modulation of glycine receptors as a new therapeutic target to confront post-ischemic injury.
甘氨酸受体(GlyRs)是细胞表面跨膜蛋白,属于 Cys 环配体门控离子通道超家族(Cys-loop LGICs)。功能性甘氨酸受体仅由α亚基(同型通道)或由α和β亚基(异型通道)组成。甘氨酸作为细胞保护剂的作用得到了广泛研究。去年出现了关于甘氨酸对血管内皮细胞(ECs)功能的调节的新信息。甘氨酸及其受体被认为通过涉及α2GlyRs 的机制发挥神经血管保护作用。有趣的是,α2GlyRs 的表达在中风损伤后减少。然而,甘氨酸通过涉及 VEGF/pSTAT3 信号的机制逆转了α2GlyRs 的抑制。另一方面,一致的证据表明 ECs 积极参与先天和适应性免疫反应。我们最近报道说,白细胞介素-1β调节甘氨酸受体,这为解释中风等病理条件下血管功能的免疫调节提供了新的视角。在这项工作中,我们区分了甘氨酸的作用和甘氨酸受体的变构调节作为对抗缺血后损伤的新治疗靶点。