Inducible nitric oxide synthase in glial cells.

Nitric oxide (NO), a free radical gas, has been suggested to mediate both synaptic plasticity and neuronal death. NO is generated by constitutive and inducible types of NO synthase (cNOS and iNOS, respectively). The neuronal cNOS was recently cloned, sequenced and characterized. In contrast, properties of iNOS in the brain are not fully understood. It is noted that glial cells can form NO and that microglial and reactive astroglial cells are accumulated around neurodegenerative sites in the brain, suggesting a relationship between neuronal injury and NO originated from glial cells. We found that several stimuli such as endotoxin (lipopolysaccharide) and cytokines induced iNOS in glial cells of rat brain. This article reviews recent findings on characteristics and the induction mechanism of iNOS in the glial cells, and discusses the possible pathophysiological functions of iNOS in the brain.