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Oxygen-radical/nitric oxide mediate calcium-dependent hormone action on cyclic GMP system: A novel concept in signal transduction mechanisms

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Abstract

The broad objective of these studies was to understand the nature of cyclic GMP system and the mechanism(s) whereby hormone, autacoids and drugs alter this signal in various physiological systems. Studies were undertaken on the modulation of guanylate cyclase activity by oxygen-radicals/nitric oxide and the mechanism(s) of generation of nitric oxide by receptor-selective hormones. We observed that cytosolic guanylate cyclase undergoes significant stimulation in the presence of oxygen-radicals/nitric oxide. This activation by nitric oxide can be reversed by hemeproteins, thus, enabling guanylate cyclase system to cycle between activated and deactivated state. The evidence is presented that oxygen-radicals are required for the synthesis of nitric oxide by NO synthase as demonstrated by inhibition of NO formation by oxygen-radical scavengers. And finally, the data is presented that acetylcholine-induced elevations of intracellular levels of cyclic GMP can be attenuated by muscarinic antagonist, atropine and superoxide anion scavenger, nitroblue tetrazolium. These observations establish a novel concept that activation of hormone receptors on the cell surface, triggers generation of oxygen radicals and hydrogen peroxide which participates in the catalytic conversion of L-arginine to nitric oxide by nitric oxide synthase in the presence of calcium ion. The oxygen-radicals/NO, thus formed, oxidatively activate guanylate cyclase and transduce the message of calcium-dependent hormones.

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References

  1. Mittal CK, Murad F: Guanylate cyclase: Regulation of cyclic GMP metabolism. In: J.A. Nathanson and J.W. Kebabian (eds.). Handbook Exptl Pharmacol, Springer Verlag, New York, 1982, vol 58/I, pp 225–260

    Google Scholar 

  2. Mittal CK: Atriopeptin II and nitrovasodilator-mediated shifts in cyclic GMP in rat thoracic aorta: Evidence for involvement of distinct guanylate cyclase pools. Eup J Pharmacol. 115: 127–128, 1985

    Google Scholar 

  3. Waldman SA, Rapoport RM, Murad F: Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem 259: 14332–14334, 1984

    PubMed  Google Scholar 

  4. Mittal CK: Actions of atrial natriuretic peptide on cyclic GMP system. Ind J Exptl Biol 25: 24–28, 1987

    Google Scholar 

  5. Murad F, Leitman D, Waldman SA, Chang CH, Hirata M, Kohse K: Effects of nitrovasodilators, endothelium-dependent vasodilators and atrial peptides on cyclic GMP. Cold Spring Harb Symp Quant Biol 53: 1005–1009, 1988

    PubMed  Google Scholar 

  6. Mittal CK, Murad F: Review: Properties and oxidative regulation of guanylate cyclase. J Cyclic Nucle Res. 3: 381–391, 1977

    Google Scholar 

  7. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev. 43: 109–142, 1991

    PubMed  Google Scholar 

  8. Ignarro W, Buga GM, Wood KS, Byrns RE, Chaudhuri G: Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Nat Acad Sci USA. 84: 9265–9269, 1987

    PubMed  Google Scholar 

  9. Ishii K, Kerwin JF, Murad F: N-Nitro-L-arginine: a potent inhibitor of the L-arginine dependent soluble guanylate activation pathway in LLC-PK1 cells. Can J Physiol Pharmacol 68: 749–751, 1990

    PubMed  Google Scholar 

  10. Kimura H, Mittal CK, Murad F: Activation of guanylate cyclase from rat liver and other tissues by sodium azide. J Biol Chem. 250: 8016–8022, 1975

    PubMed  Google Scholar 

  11. Mittal CK, Kimura H, Murad F: Requirement of a macromolecular factor for sodium azide activation of guanylate cyclase. J Cyclic Nucleot Res. 1: 261–269, 1975

    Google Scholar 

  12. Kimura H, Mittal CK, Murad F: Increases in cyclic GMP levels in brain and liver with sodium azide-an activator of guanylate cyclase. Nature 257: 700–702, 1975

    PubMed  Google Scholar 

  13. Mittal CK, Kimura H, Murad F: Purification and properties of a protein factor required for sodium azide activation of guanylate cyclase. J Biol Chem 252: 4384–4390, 1977

    PubMed  Google Scholar 

  14. Forstermann U, Schmidt HHHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F: Isoforms of nitric oxide synthase: Characterization and purification from different cell types. Biochem Pharmacol 42: 1849–1857, 1991

    PubMed  Google Scholar 

  15. Keilin D, Hartree EF: Reactions of methemoglobin and catalase with peroxide and hydrogen donors. Nature 173: 720–723, 1954

    PubMed  Google Scholar 

  16. Arnold WP, Mittal CK, Katsuki S, Murad F: Nitric oxide activates guanylate cyclase and increases cyclic GMP levels in various tissue preparations. Proc Nat Acad Sci USA 74: 3203–3207, 1977

    PubMed  Google Scholar 

  17. Katsuki S, Arnold WP, Mittal CK, Murad F: Stimulation of gyanylate cyclase by sodium nitroprusside, nitroglycerine and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucl Res 3: 1829–1833, 1977

    Google Scholar 

  18. Mittal CK, Murad F: Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: A physiological regulator of guanosine 3′, 5′-monophosphate. Proc Nat Acad Sci USA 74: 4360–4364, 1977

    PubMed  Google Scholar 

  19. Mittal CK, Arnold WP, Murad F: Characterization of protein inhibitors of guanylate cyclase activation from rat heart and bovine lung. J Biol Chem 253: 1266–1271, 1978

    PubMed  Google Scholar 

  20. Martin W, Villani GM, Jothianandan D, Furchgott RF: Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther 232: 708–716, 1985

    PubMed  Google Scholar 

  21. Mittal CK, Murad F: Formation of adenosine 3′, 5′-monophosphate by preparations of guanylate cyclase from rat liver and other tissues. J Biol Chem 252: 3136–3140, 1977

    PubMed  Google Scholar 

  22. Mittal CK, Braughler JM, Ichihara K, Murad F: Synthesis of adenosine 3′, 5′ monophosphate by guanylate cyclase, A new pathway for its formation. Biochim Biophys Acta 585: 333–342, 1979

    PubMed  Google Scholar 

  23. Deguchi T, Yoshioka M: L-Arginine identified as an endogenous activator for soluble guanylate cyclase from neuroblastoma cells. J Biol Chem 257: 10147–10151, 1982

    PubMed  Google Scholar 

  24. Hibbs JD, Vavrin Z, Taintor RR: L-Arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol 138: 550–565, 1987

    PubMed  Google Scholar 

  25. Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS: Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 21: 8706–8711, 1988

    Google Scholar 

  26. Palmer RMJ, Moncada S: A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 158: 348–352, 1989

    PubMed  Google Scholar 

  27. Knowles RG, Palacios M, Palmer RMJ, Moncada S: Formation of nitric oxide from L-arginine in the central nervous system: A transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Nat Acad Sci USA 86: 5159–5162, 1989

    PubMed  Google Scholar 

  28. Gorsky LD, Forstermann U, Ishii K, Murad F: Production of an EDRF-like activity in the cytosol of NIE-115 neuroblastoma cells. FASEB J 4: 1494–1500, 1990

    PubMed  Google Scholar 

  29. Mittal CK: Nitric oxide synthase: Involvement of oxygen radicals in conversion of L-arginine to nitric oxide. Biochem Biophys Res Commun 193: 126–132, 1993

    PubMed  Google Scholar 

  30. Pou S, Pou WS, Bredt DS, Snyder SH, Rosen GM: Generation of superoxide by purified nitric oxide synthase J Biol Chem 267: 24173–24176, 1992

    PubMed  Google Scholar 

  31. Heinzel B, John M, Klatt P, Bohme E, Mayer B: Calcium/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthesis. Biochem J 281: 627–630, 1992

    PubMed  Google Scholar 

  32. Murad F, Ishii K, Gorsky L, Forstermann U, Kerwin JF, Heller M: Endothelium derived relaxing factor is a ubiquitous intracellular second messenger and extracellar paracrine substance for cyclic GMP synthesis. In: S. Moncada and E.A. Higgs (eds). Nitric oxide from L-arginine: a bioregulatory system, Elsevier Science Publishers B.V, 1990, pp 301–315

  33. Dimmeler S, Lottspeich F, Brune B: Nitric oxide causes ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem 267: 16771–16774, 1992

    PubMed  Google Scholar 

  34. Sitmann JV, Cahill PA: Regulation of angiotensin 11 receptors by nitric oxide in rat vascular smooth muscle cells. FASEB J 8: A595, 1994

    Google Scholar 

  35. Hope BT, Michael GJ, Knigge KM, Vincent SR: Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Nat Acad Sci USA 88: 2811–2814, 1991

    PubMed  Google Scholar 

  36. Klatt P, Heinzel B, John M, Kastner M, Bohme E, Mayer B: Ca/calmodulin dependent cytochrome C reductase activity of brain nitric oxide synthase. J Biol Chem 267: 11374–11378, 1992

    PubMed  Google Scholar 

  37. Mittal CK: Measurements of cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in polymorphonuclear leukocytes, macrophages, and lymphocytes. In: G.D. Sabato and J. Everse (eds). Methods in Enzymol, Acad Press, NY, 1986, vol 132, pp 428–434

    Google Scholar 

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  1. Division of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, 77004, Houston, Texas, USA

    Chandra K. Mittal

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Mittal, C.K. Oxygen-radical/nitric oxide mediate calcium-dependent hormone action on cyclic GMP system: A novel concept in signal transduction mechanisms. Mol Cell Biochem 149, 257–262 (1995). https://doi.org/10.1007/BF01076585

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