Role of Glycine and Glycine Receptors in Vascular Endothelium: A New Perspective for the Management of the Post-Ischemic Injury

Glycine Receptors (GlyRs) are cell-surface transmembrane proteins that belong to the Cys-loop ligand-gated ion channels superfamily (Cys-loop LGICs). Functional glycine receptors are conformed only by alpha-subunits (homomeric channels) or by alpha- and beta-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 alpha 2GlyRs. Interestingly, the expression of alpha 2GlyRs reduces after stroke injury. However, glycine reverses the inhibition of alpha 2GlyRs 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-1 beta, 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.