The interactions between nitric oxide and brain nerve terminals as studied by electron paramagnetic resonance.
It has been proposed that nitric oxide (NO) toxicity is due to damage to mitochondrial iron-sulfur centers, resulting in inhibition of mitochondrial respiration and the appearance of an EPR-detectable (g = 2.04) iron-sulfur dinitrosyl complex - Fe(RS)2(NO)2. We show that the addition of nitroprusside (an NO and NO+ donor) to rat brain synaptosomes generates large (> 30 microM) concentrations of EPR-detectable iron-sulfur-dinitrosyl complexes. However, there was no correlation between the size of the g = 2.04 EPR signal and the inhibition of synaptosomal respiration. No significant loss of intensity was seen from the mitochondrial iron-sulfur protein EPR signals. The results are consistent with previous data demonstrating that cytochrome oxidase, not iron-sulfur enzymes, is the primary target for NO inhibition of brain cell respiration (Brown, G.C. and Cooper, C.E. (1994) FEBS Lett. 356, 295-298).
Cooper
C E
CE
Department of Paediatrics, University College London Medical School, Rayne Institute, UK.
Brown
G C
GC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure*; D004578:Electron Spin Resonance Spectroscopy; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D007506:Iron-Sulfur Proteins; D009599:Nitroprusside; D009569:Nitric Oxide