Nitric oxide alters metabolism in isolated alveolar type II cells.
Alveolar type II cells may be exposed to nitric oxide (.NO) from external sources, and these cells can also generate .NO. Therefore we studied the effects of altering .NO levels on various type II cell metabolic processes. Incubation of cells with the .NO generator, S-nitroso-N-acetylpenicillamine (SNAP; 1 mM), leads to reductions of 60-70% in the synthesis of disaturated phosphatidylcholines (DSPC) and cell ATP levels. Cellular oxygen consumption, an indirect measure of cell ATP synthesis, is also reduced by SNAP. There is no direct effect of SNAP on lung mitochondrial ATP synthesis, suggesting that .NO does not directly inhibit this process. On the other hand, incubation of cells with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for .NO synthesis, results in increases in DSPC synthesis, cell ATP content, and cellular oxygen consumption. The L-NAME effects are reversed by addition of L-arginine, the substrate for NOS. Production of .NO by type II cells is inhibited by L-NAME, a better inhibitor of constitutive NOS (cNOS) than inducible NOS (iNOS), and is reduced in the absence of external calcium. Aminoguanidine, a specific inhibitor of iNOS, has no effect on cell ATP content or on .NO production. These results indicate that alveolar type II cell lipid and energy metabolism can be affected by .NO and suggest that there may be cNOS activity in these cells.
Miles
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PR
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. PRMI@NIORDS1.EM.CDC.GOV
Bowman
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Huffman
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002469:Cell Separation; D002794:Choline / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D010101:Oxygen Consumption; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine
D010713:Phosphatidylcholines; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D000255:Adenosine Triphosphate; D010396:Penicillamine; D002794:Choline