Effect of carbon monoxide on dopamine and glutamate uptake and cGMP levels in rat brain.

After the recognition of nitric oxide (NO) as a messenger molecule in the nervous system, carbon monoxide (CO) has received attention with similar properties. The present study aims to elucidate the effects of CO on synaptosomal dopamine ((3)H-DA) and glutamate ((3)H-Glu) uptake and on cGMP levels; possible interaction between NO and CO systems was also evaluated. Our results provide evidence for the inhibition of DA and Glu uptake by CO in a time-, dose-, and temperature-dependent manner in rat striatum and hippocampus, respectively; the inhibition observed was sexually dimorphic with more pronounced effects in females. Basal cGMP levels were higher in female rats than males in the striatum and exogenous CO increased striatal cGMP levels only in males; no effect of CO was observed in the hippocampus. In vivo nitric oxide synthase (NOS) inhibition increased DA and Glu uptake; however, CO was still effective in inhibiting uptake following NOS inhibiton. Taken together, these findings suggest a role for CO in trans-synaptic regulation through modulation of DA and Glu transporters and of cGMP levels; the effect on cGMP levels is independent of NOS activity and appears to be sexually dimorphic and region specific.