Alcohol and nitric oxide production by cells of the brain

The L-arginine-nitric oxide pathway is important to both physiological and pathologic brain events. Brain tissue contains cells able to express all known isoforms of nitric oxide synthase, the rate-limiting enzyme in nitric oxide (NO) production and release. Effects of ethanol on NO production may be important to ethanol modification of brain function. Recent studies support this idea and demonstrate diverse interactions. For example, acute ethanol treatment decreases NMDA- and cytokine-stimulated NO synthesis by cortical neurons and glia, respectively, but enhances cytokine-stimulated NO synthesis in blood-brain barrier endothelial cells and does not affect norepinephrine-stimulated NO synthesis in medial basal hypothalamus. Furthermore, chronic ethanol enhances NMDA-stimulated NO synthesis in cortical neurons, but more potently decreases cytokine-induced NO synthesis in glial cells. The mechanisms underlying these effects are partially understood and include changes in NOS-2 gene expression. These observations illustrate that ethanol selectively affects NO production by brain cells, which may relate to reported behavioral interactions, but the extend and direction of change depends on cell type and length of exposure.