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Nitric Oxide Synthase Inhibition by L-NAME Prevents the Decrease of Na+,K+-ATPase Activity in Midbrain of Rats Subjected to Arginine Administration

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Abstract

In the present study we investigated the effect of acute administration of L-arginine on Na+,K+-ATPase and Mg2+-ATPase activities and on some parameters of oxidative stress (chemiluminescence and total radical-trapping antioxidant parameter-TRAP) in midbrain of adult rats. We also tested the effect of L-NAME on the effects produced by arginine. Sixty-day-old rats were treated with an acute intraperitoneal injection of saline (group I, control), arginine (0.8 g/kg) (group II), L-NAME (2 mg/kg) (group III) or arginine (0.8 g/kg) plus L-NAME (2 mg/kg) (group IV). Na+,K+-ATPase activity was significantly reduced in the arginine-treated rats, but was not affected by other treatments. In contrast, Mg2+-ATPase activity was not altered by any treatment. Furthermore, chemiluminescence was significantly increased and TRAP was significantly decreased in arginine-treated rats, whereas the simultaneous injection of L-NAME prevented these effects. These results demonstrate that in vivo arginine administration reduces Na+,K+-ATPase activity possibly through free radical generation induced by NO formation.

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REFERENCES

  1. Brusilow, S. W. and Horwich, A. 2001. Urea cycle enzymes. Pages 1909–1963, In: Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D. (eds), The Metabolic and Molecular Bases of Inherited Disease, 8th Ed, McGraw-Hill, Inc., New York.

    Google Scholar 

  2. Iyer, R., Jenkinson, C. P., Vockley, J. G., Kern, R. M., Grody, W. W., and Cederbaum, S. 1998. The human arginases and arginase deficiency. J. Inher. Metab. Dis. 21:86–100.

    Google Scholar 

  3. Lincoln, J., Hoyle, C. H. V., and Burnstock, G. 1997. Nitric oxide in health and disease, Biochemical Research Topics. Cambridge University Press, Cambridge.

    Google Scholar 

  4. Beckmam, J. S., Carson, M., Smith, C. D., and Koppenol, W. H., 1993. ALS, SOD and peroxynitrite. Nature 364, 584.

    Google Scholar 

  5. Lipton, S. A., Choi, Y. B., Pan, Z. H., Lei, S. Z., Chen, H. S. V., Sucher, N. J., Loscalzo, J., Singel, D. J., and Stamler, J. S. 1993. A redox basead mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso compounds. Nature 364:626–632.

    Google Scholar 

  6. Dawson, V. L. and Dawson, T. M. 1996. Nitric oxide neurotoxicity. J. Chem. Neuroanat. 10:179–190.

    Google Scholar 

  7. Heales, S. J. R., Bolaños, J. P., Stewart, V. C., Brookes, P. S., Land, J. M., and Clark, J. B. 1999. Nitric oxide, mitochondria and neurological disease. Biochim. Biophys. Acta 1410:215–228.

    Google Scholar 

  8. Sarti, P., Lendaro, E., Ippoliti, R., Benedetti, P. A., and Brunori, M. 1999. Modulation of mitochondrial respiration by nitric oxide: investigation by single cell fluorescence microscopy. FASEB J. 13:191–197.

    Google Scholar 

  9. Brunori, M. 2001. Nitric oxide, cytochrome-c oxidase and myoglobin. Trends Biochem. Sci. 26:21–23.

    Google Scholar 

  10. Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S., and Snyder, S. H. 1991. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl. Acad. Sci. 88:6386–6371.

    Google Scholar 

  11. Almeida, A., Heales, S. J. R., Bolanos, J. P., and Medina, J. M. 1998. Glutamate neurotoxicity is asociated with nitric oxidemediated mitochondrial dysfunction and glutathione depletion. Brain Res. 790:209–216.

    Google Scholar 

  12. Dawson, T. M., Hung, K., Dawson, V. L., Steiner, J. P., and Snyder, H. S. 1995. Neuroprotective effects of gangliosides may involve inhibition of nitric oxide synthase. Ann. Neurol. 37: 115–118.

    Google Scholar 

  13. Radi, R., Beckman, J. S., Bush, K. M., and Freeman, B. A. 1991. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys. 288:481–487.

    Google Scholar 

  14. Moreno, J. J. and Pryor, W. A. 1995. Inactivation of 1-proteinase inhibitor by peroxynitrite. Chem. Res. Toxicol. 5:425–431.

    Google Scholar 

  15. King, P. A., Adnerson, V. E., Edwards, J. O., Gustafson, G., Plumb, R. C., and Suggs, J. W. 1992. A stable solid that generates hydroxyl radical upon dissolution in aqueous solution: reaction with proteins and nucleic acids. J. Am. Chem. Soc. 114:5430–5432.

    Google Scholar 

  16. Ericinska, M. and Silver, I. A. 1994. Ions and energy in mammalian brain. Prog. Neurobiol. 43:37–71.

    Google Scholar 

  17. Lees, G. J. 1993. Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience 54:287–322.

    Google Scholar 

  18. Sato, T., Kamata, Y., Irifune, M., and Nishikawa, T. 1995. Inhibition of purified (Na+,K+)-ATPase activity from porcine cerebral cortex by NO generating drugs. Brain Res. 704:117–120.

    Google Scholar 

  19. Avrova, N. F., Shestak, K. I., Zakharova, I. O., Sokolova, T. V., and Leont'ev, V. G. 1999. The difference in the effect of glutamate and NO synthase inhibitor on free calcium concentration and Na+,K+-ATPase activity in synaptosomes from various brain regions. Neurochem. Res. 24:1101–1106.

    Google Scholar 

  20. Silva, C. G., Parolo, E., Streck, E. L., Wajner, M., Wannmacher, C. M. D., and Wyse, A. T. S. 1999. In vitro inhibition of Na+,K+-ATPase activity from rat cerebral cortex by guanidino compounds accumulating in hyperarginemia. Brain Res. 838:78–84.

    Google Scholar 

  21. Buchmann, I., Milakofsky, L., Harris, N., Hofford, J. M., and Vogel, W. H. 1996. Effect of arginine administration on plasma and brain levels of arginine and various related amino compounds in the rat. Pharmacology 53:133–142.

    Google Scholar 

  22. Nishikawa, T., Kirsch, J. R., Koehler, R. C., Bredt, S. D., Snyder, S. H., and Traystman, R. J. 1993. Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats. Stroke 24:1718–1724.

    Google Scholar 

  23. Buisson, A., Plotkine, M., and Boulu, R. G. 1992. The neuroprotective effect of a nitric oxide inhibitor in a rat model of focal cerebral ischaemia. Br. J. Pharmacol. 106:766–767.

    Google Scholar 

  24. Jones, D. H. and Matus, A. I. 1974. Isolation of synaptic plasma membrane from brain by combined flotation-sedimentation density gradient centrifugation. Biochim. Biophys. Acta 356: 276–287.

    Google Scholar 

  25. Tsakiris, S. and Deliconstantinos, G. 1984. Influence of phosphatidylserine on (Na+ + K+)-stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes. Biochem. J. 22:301–307.

    Google Scholar 

  26. Chan, K. M., Delfert, D., and Junger, K. D. 1986. A direct colorimetric assay for Ca+2-stimulated ATPase activity. Anal. Biochem. 157:375–380.

    Google Scholar 

  27. Gonzalez-Flecha, B., Llesuy, S., and Boveris, A. 1991. Hydroperoxide-initiated chemiluminescence: an assay for oxidative stress in biopsies of heart, Liver and muscle. Free Rad. Biol. Med. 10:93–100.

    Google Scholar 

  28. Lissi, E., Pascual, C., and Del Castillo, M. D. 1992. Luminol luminescence induced by 2-2′-Azo-bis(2-amidinopropane) thermolysis. Free Rad. Res. Commun. 17:299–311.

    Google Scholar 

  29. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-die binding. Anal. Biochem. 72: 248–254.

    Google Scholar 

  30. Jensen, J. and Nörby, J. G. 1988. Membrane-bound Na+,K+-ATPase: target size and radiation inactivation size of some of its enzymatic reactions. J. Biol. Chem. 263:18063–18070.

    Google Scholar 

  31. Boldyrev, A. A., Lopina, O. D., and Fedesova, N. U. 1990. Na+,K+-ATPase: radiation inactivation studies. Biochem. Int. 21:45–52.

    Google Scholar 

  32. Beckman, J. S. and Koppenol, W. H. 1996. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am. J. Physiol. 271:1424–1427.

    Google Scholar 

  33. Rubbo, H., Radi, R., Trujillo, M., Telleu, R., Kalyanaramam, B., Bornes, S., Kirk, M., and Freeman, B. A. 1994. Nitric oxide regulation of superoxide and peroxinitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J. Biol. Chem. 269:26066–26075.

    Google Scholar 

  34. Brown, G. C. 1995. Reversible binding and inhibition of catalase by nitric oxide. Eur. J. Biochem. 232:188–191.

    Google Scholar 

  35. Asahi, M., Fujii, J., Suzuki, K., Seo, H. G., Kuzuya, T., Hori, M., Tada, M., Fujii, S., and Taniguchi, N. 1995. Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity. J. Biol. Chem. 270:1035–21039.

    Google Scholar 

  36. Luperchio, S., Tamir, S., and Tannembaum, S. R. 1996. NO-induced oxidative stress and glutathione metabolism in rodent and human cells. Free Rad. Biol. Med. 21:513–519.

    Google Scholar 

  37. Lees, G. J. 1991. Inhibition of sodium-potassium-ATPase: a potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res. Rev. 16:283–300.

    Google Scholar 

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Authors and Affiliations

  1. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, R, S, Brazil

    Angela Terezinha de Souza Wyse, Caren Serra Bavaresco, Cintia Bandinelli, Emílio Luiz Streck, Renata Franzon, Carlos Severo Dutra-Filho & Moacir Wajner

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  1. Angela Terezinha de Souza Wyse
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de Souza Wyse, A.T., Bavaresco, C.S., Bandinelli, C. et al. Nitric Oxide Synthase Inhibition by L-NAME Prevents the Decrease of Na+,K+-ATPase Activity in Midbrain of Rats Subjected to Arginine Administration. Neurochem Res 26, 515–520 (2001). https://doi.org/10.1023/A:1010912929042

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