Microglial cells are considered as the macrophages of the brain. Besides this immune function, recent data suggest that they could play an important role in neuronal development and synaptogenesis as wells as in various neuropathological conditions. Glycine is best known as the neurotransmitter mediating fast inhibitory neurotransmission in the caudal part of the central nervous system. Glycine has also been proposed as an immunomodulatory signal for various immune cells. Several studies suggested that this modulation is dependent on Glycine Receptors (GlyRs), in general causing an inhibition of the immune function. In microglia, it has been shown that astrocyte-derived glycine modulates microglial activity, although the mechanism is unknown. The aim of this work was to determine the role of GlyRs in this microglial immunomodulation. Two in vitro models were used: the mouse microglial BV-2 cell line and primary microglial cultures derived from newborn rats. By means of western blotting and immunocytochemistry, we found molecular evidence for GlyRs in both cell types. RT-PCR data showed that these receptors were composed of a1, a3 and b-subunits.

Nitrogen oxide production was significantly enhanced by micromolar concentrations of glycine (EC₅₀=30mM) as determined in cell culture supernatants by the Griess assay. This stimulatory effect was not blocked by GlyR antagonists (strychnine and picrotoxinine), nor could it be mimicked by GlyR agonists (b-alanine and taurine) suggesting a GlyR-independent mechanism.

Our data suggest that glycine is an important modulator of NO production in microglial cells. This effect does not seem to be mediated by GlyRs, as has been suggested for many other immune cells (e.g. T lymphocytes, macrophages, ...). Further research is necessary to unravel the precise mechanism of this effect, which may be interesting as a potential new therapeutic target.