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 neurons, functions as a diffusible intercellular messenger and appears to play a role in activity-dependent modification of synaptic efficacy in the mammalian CNS. The molecular targets and mechanisms of action of NO in neurons remain largely uncharacterized. Employing in vitro brain slices and isolated synaptosomes, we show here that exposure to exogenous or endogenously generated NO results in the modification of cysteine residues within neuronal proteins, as revealed by reduced binding of agents which react with cysteine sulfhydryls. In particular, exposure of synaptosomes to NO inhibits subsequent thiol-linked ADP-ribosylation of the heterotrimeric G-protein, G(o), by pertussis toxin. Our results demonstrate directly that NO may exert its neuronal effects through modification of protein cysteine thiols, and identify G(o) as a potential synaptic target of NO.
Hess
D T
DT
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Lin
L H
LH
Freeman
J A
JA
Norden
J J
JJ
D000818:Animals; D002417:Cattle; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007460:Iodoacetamide / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D037342:Pertussis Toxin; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D010566:Virulence Factors, Bordetella; D009569:Nitric Oxide; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D008628:Mercury; D003545:Cysteine; D004229:Dithiothreitol; D007460:Iodoacetamide