Nitric Oxide: A Novel Intercellular Messenger in the Striatum

The free radical gas nitric oxide (NO) has recently been proposed as a messenger, or novel type of neurotransmitter in the brain (Bredt et al., 1991; Snyder and Bredt, 1992). The initial evidence for a role for NO in the central nervous system came when Garthwaite et al (1988) showed that cerebellar neurones would synthesize NO in response to the excitatory neurotransmitter glutamate, an observation confirmed by Bredt and Snyder (1989) amongst others. Subsequent work by Bredt and Snyder (1990) characterized the enzyme responsible for nitric oxide production, nitric oxide synthase (NOS) from rat brain and they cloned and isolated NOS (Bredt et al., 1991). The cloning and isolation of brain NOS revealed that the enzyme was structurally related only to cytochrome P450-oxido-reductase (CP-450 OR) which like NOS has an electron-transferring/accepting carboxy-terminal sequence (Bredt et al., 1991). The ability of NOS to reduce the dye nitro-blue tetrazolium accounting for a significant amount of brain diaphorase activity and diaphorase staining reflects NOS containing neurones (Figure 1) (Hope et al., 1991). We have confirmed these observations using in situ hybridization with antisense probes for NOS and NOS specific antibodies which visualize the same population of neurones in the brain and striatum (Figure 1).