Investigations into the mechanism of action of a novel nitric oxide generator on cellular respiration.
Nitric oxide may regulate cellular respiration by competition with oxygen at mitochondrial cytochrome oxidase. Using an astrocyte-derived cell line, we have compared the mechanism of action of the nitric oxide-generating compound Roussin's black salt with that of sodium nitroprusside on cellular oxygen consumption. Intense light exposure induced the release of large quantities of nitric oxide from both of the donor compounds. However, in room light only Roussin's black salt generated low levels of the radical. Simultaneous measurement of oxygen consumption and of nitric oxide production demonstrated that sodium nitroprusside only had inhibitory actions when exposed to intense light (nitric oxide release), whereas Roussin's black salt had inhibitory actions in room light. Extracellular haemoglobin did not prevent the inhibition of respiration rate induced by Roussin's black salt even though stimulation of nitric oxide release on light exposure was markedly reduced. Preincubation of cells with Roussin's black salt and subsequent measurement of levels of light-liberated nitric oxide demonstrated that the compound was rapidly internalised. The uptake of sodium nitroprusside was minimal. These data suggest that, in contrast to sodium nitroprusside, the cellular internalisation of Roussin's black salt allows site-directed nitric oxide release and very effective inhibition of cellular respiration.
Hurst
R D
RD
Department of Neurochemistry, Institute of Neurology, London, England.
Chowdhury
R
R
Clark
J B
JB
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D005910:Glioma; D006454:Hemoglobins / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D058085:Iron Compounds; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism*; D009599:Nitroprusside / Q000493:pharmacokinetics / Q000494:pharmacology; D009603:Nitroso Compounds; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology
D006454:Hemoglobins; D007502:Iron Chelating Agents; D058085:Iron Compounds; D009603:Nitroso Compounds; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C078952:Roussin's Black Salt; D007770:L-Lactate Dehydrogenase; D010100:Oxygen