Dt. Hess et al., MODIFICATION OF CYSTEINE RESIDUES WITHIN G(O) AND OTHER NEURONAL PROTEINS BY EXPOSURE TO NITRIC-OXIDE, Neuropharmacology, 33(11), 1994, pp. 1283-1292
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.