COMMENTARY - NITRIC OXIDE PRECURSOR ARGININE AND S-NITROSOGLUTATHIONEIN SYNAPTIC AND GLIAL FUNCTION

In the last few years, there has been an important increase in interes t in nitric oxide (NO) as an intercellular messenger, and its putative role in numerous CNS functions is being continually updated. Arginine , the nitric oxide precursor, has been found in our laboratory to be r eleased following stimulation of the white matter in the cerebellum an d of sensory afferents in the thalamus. Since arginine is localized in glial cells while the nitric oxide synthesizing enzyme is localized i n different cells (predominantly in neurons), these findings may repre sent a transfer of arginine from glia to neurons in order to supply th e nitric oxide synthase with its substrate. The mechanism underlying t his glial-neuronal interaction seems to involve the activation of exci tatory amino acid receptors present on glial cells. Our results speak for an intense crosstalk between neurons and glia (activation of glial receptors by neurotransmitter released from neurons) and between glia and neurons (supply of the nitric precursor arginine from glia to neu rons). The form in which NO is released from cells has been much debat ed. The chemical identity of the endothelial-derived relaxing factor i n particular is still a matter of dispute, the major contender being N O. and a S-nitrosothiol compound. Based on the strong reactivity of NO for thiols and on the presence of cysteine and glutathione at the mM level intracellularly and mu M level extracellularly, we have investig ated whether S-nitrosothiols, i.e. S-nitrosoglutathione, may be the po tential ''package'' form in which NO could be stored. We demonstrated, with HPLC coupled to mass spectrometry techniques, the presence of en dogenous nitrosoglutathione in rat brain tissue. This packaging of NO in the form of nitrosothiols might serve to facilitate its transfer, p rolong its life, and target its delivery to specific effecters. That c ould confer a specificity of action to the widely diffusable messenger NO, may determine the range of effectiveness of NO and mitigate its a dverse cytotoxic effects. Copyright (C) 1996 Elsevier Science Ltd.