The metabolic coupling of arginine metabolism to nitric oxide generation by astrocytes

Arginine, the only known precursor of nitric oxide, enters the brain parenchyma from the blood through the endothelial cells or from the cerebral spinal fluid through the ependymal cells. Astrocytes, whose processes abut the endothelium and ependymum, take up arginine through cationic amino acid transporters and release arginine through this transport system to the synapses that astrocytes shield. Some of these synapses are excitatory, and liberate glutamate into the synaptic cleft. Glutamate induces arginine release from astrocytes, making it available to the neuron. Neurons can take up arginine to be used in nitric oxide-mediated processes, such as neurotransmission. Thus, neural and nonneural cells act in concert to affect neuron physiology in an elegantly integrated system. This review focuses on the components of the interaction between astrocytes and neurons in nitric oxide biology.