MODIFICATION OF CYSTEINE RESIDUES WITHIN G(O) AND OTHER NEURONAL PROTEINS BY EXPOSURE TO NITRIC-OXIDE

Nitric oxide (NO), a free-radical gas produced endogenously by some ne urons, functions as a diffusible intercellular messenger and appears t o play a role in activity-dependent modification of synaptic efficacy in the mammalian CNS. The molecular targets and mechanisms of action o f NO in neurons remain largely uncharacterized. Employing in vitro bra in slices and isolated synaptosomes, we show here that exposure to exo genous or endogenously generated NO results in the modification of cys teine residues within neuronal proteins, as revealed by reduced bindin g of agents which react with cysteine sulfhydryls. In particular, expo sure of synaptosomes to NO inhibits subsequent thiol-linked ADP-ribosy lation of the heterotrimeric G-protein, G(0), by pertussis toxin. Our results demonstrate directly that NO may exert its neuronal effects th rough modification of protein cysteine thiols, and identify G(0) as a potential synaptic target of NO.