Glycine and glycine receptor signalling in non-neuronal cells

Abstract

Glycine is an inhibitory neurotransmitter acting mainly in the caudal part of the central nervous system. Besides this neurotransmitter function, glycine has cytoprotective and modulatory effects in different non-neuronal cell types. Modulatory effects were mainly described in immune cells, endothelial cells and macroglial cells, where glycine modulates proliferation, differentiation, migration and cytokine production. Activation of glycine receptors (GlyRs) causes membrane potential changes that in turn modulate calcium flux and downstream effects in these cells. Cytoprotective effects were mainly described in renal cells, hepatocytes and endothelial cells, where glycine protects cells from ischemic cell death. In these cell types, glycine has been suggested to stabilize porous defects that develop in the plasma membranes of ischemic cells, leading to leakage of macromolecules and subsequent cell death. Although there is some evidence linking these effects to the activation of GlyRs, they seem to operate in an entirely different mode from classical neuronal subtypes.

Glycine enhances microglial intracellular calcium signaling. A role for sodium-coupled neutral amino acid transporters

“…This modulation was shown to be GlyR-independent, contrary to the previously shown modulation of glycine on calcium transients in peripheral macrophages [33]. We demonstrate further that this modulation can be mimicked by some structurally related neutral amino acids (e.g., serine, alanine, or glutamine), is inhibited by the neutral Fig.…”

“…In non-neuronal cells, glycine was shown to protect different cell types against ischemic cell death (e.g., renal cells, hepatocytes, and endothelial cells). Furthermore, glycine was shown to have modulatory properties in glial cells (astrocytes, oligodendrocytes, and microglia), immune cells, and sperm cells, as reviewed recently [33]. The immunomodulatory properties were best studied in Kupffer cells, the resident macrophages of the liver, where an inhibition of cytokine production (e.g., tumor necrosis factor α) was found, explaining beneficial glycine effects in animal models of alcohol hepatitis and endotoxic shock [11,12,37].…”

Bioinformatic Analyses of Renal Ischaemia-Reperfusion Injury Models: Identification of Key Genes Involved in the Development of Kidney Disease

“…Dimethylglycine dehydrogenase, encoded by Dmgdh, is a mitochondrial matrix enzyme involved in the metabolism of choline to glycine [34]. Glycine was reported to possess anti-inflammatory and immunomodulatory roles against ischaemia-induced renal injury [35]. In fact, glycine protected against mild unilateral IRI (15 min ischaemia) [36].…”

Vascular endothelial function is improved by oral glycine treatment in aged rats

“…Glycine acts in the central nervous system as an inhibitory neurotransmitter via glycine receptors (GlyRs). The GlyRs are also localised on nonneuronal cells, such as Kupffer cells, alveolar macrophages, neutrophils, and endothelial cells (Van den Eynden et al 2009). In type 2 diabetes, glycine treatment decreases glycated haemoglobin (Carvajal et al 1999;Cruz et al 2008).…”