Modulation of nitric oxide production in vivo in the brain

Nitric oxide (NO) is a free radical gas that is synthesized from L-arginine (L-Arg) by NO synthase (NOS). Activation of N-methyl-D-aspartate (NMDA), non-NMDA or metabotropic glutamate receptor (mGluR) causes NO formation through NOS activation. We propose that there may be two pathways for NO production; NOS-dependent and independent pathways. Activation of NMDA receptors results in an increase in NO production via the NOS-dependent pathways whereas activation of non-NMDA receptors or mGluR may produce NO through not only the NOS-dependent pathway but also an NOS-independent pathway. Furthermore, it is suggested that glial cells may play a role in modulating NO production by regulating L-Arg availability.