Skip to main content
SpringerLink
Log in

Nitric Oxide Synthase

  • Chapter
Reactive Oxygen Species in Biological Systems

  • 404 Accesses

Conclusions

The discovery of the L–arginine:NO pathway has proven to be one of the most important and exciting scientific developments of the last decade. This pathway is involved in a myriad of physiologic roles that range from the control of vascular tone and blood pressure to the modulation of skeletal muscle function. An increasing number of pathological conditions are now being recognized to be the result of either excessive or insufficient NO production. Intensive efforts are being dedicated to the development of selective NOS inhibitors with the hope of targeting specific tissue sources of excessive NO production. Similarly, genetic approaches to treat conditions resulting from reduced NOS expression are likely to be explored in the near future. New developments in the field of NO research are likely to continue at the current rapid pace. This should bring important additional benefits to most areas of clinical medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adachi, H., Iida, S., Oguchi, S., Ohshima, H., Suzuki, H., Nagasaki, K., Kawasaki, H., Sugimura, T., and Esumi, H., 1993, Molecular cloning of a cDNA encoding an inducible calmodulin-dependent nitric-oxide synthase from rat liver and its expression in COS-1 cells, Eur. J. Biochem. 217:37–43.

    Article  CAS  PubMed  Google Scholar 

  • Adcock, I. M., Brown, C. R., Kwon, O., and Barnes, P. J., 1994, Oxidative stress induces NF kappa b DNA binding and inducible NOS messenger RNA in human epithelial cells, Biochem. Biophys. Res. Commun. 199:1518–1524.

    Article  CAS  PubMed  Google Scholar 

  • Albakri, Q. A., and Stuehr, D. J., 1996, Intracellular assembly of inducible NO synthase is limited by nitric oxide-mediated changes in heme insertion and availability, J. Biol. Chem. 271:5414–5421.

    CAS  PubMed  Google Scholar 

  • Amoah-Apraku, B., Chandler, L. J., Harrison, J., Tang, S. S., Ingelfinger, J. R., and Guzman, N. J., 1995a, NF-κ and transcriptional control of renal epithelial inducible nitric oxide synthase. Kidney Int. 48:674–682.

    CAS  PubMed  Google Scholar 

  • Amoah-Apraku, B., Tang, S. S., Ingelfinger, J. R., and Guzman, N. J., 1995b, Guanosine triphosphate cyclohydrolase I regulates nitric oxide synthesis in renal proximal tubules, J. Am. Soc. Nephrol. 5:1630–1633.

    CAS  PubMed  Google Scholar 

  • Anagli, J., Hofmann, F., Quadroni, M., Vorherr, T., and Carafoli, E., 1995, The calmodulin-binding domain of the inducible (macrophage) nitric oxide synthase, Eur. J. Biochem. 233:701–708.

    Article  CAS  PubMed  Google Scholar 

  • Aneman, A., Backman, V., Snygg, J., Vonbothmer, C., Fandriks, L., and Pettersson, A., 1994, Accumulation of an endogenous inhibitor of nitric oxide synthase during graded hemorrhagic shock, Circ. Shock 44:111–114.

    CAS  PubMed  Google Scholar 

  • Aranow, J. S., Zhuang, J., Wang, H. L., Larkin, V., Smith, M., and Fink, M. P., 1996, A selective inhibitor of inducible nitric oxide synthase prolongs survival in a rat model of bacterial peritonitis: Comparison with two nonselective strategies, Shock 5:116–121.

    CAS  PubMed  Google Scholar 

  • Arnet, U. A., McMillan, A., Dinerman, J. L., Ballermann, B., and Lowenstein, C. J., 1996, Regulation of endothelial nitric-oxide synthase during hypoxia, J. Biol. Chem. 271:15069–15073.

    CAS  PubMed  Google Scholar 

  • Auphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., and Karin, M., 1995, Immunosuppression by glucocorticoids: Inhibition of NF-κ through induction of I-KB synthesis, Science 270:286–290.

    CAS  PubMed  Google Scholar 

  • Bates, T. E., Loesch, A., Burnstock, G., and Clark, J. B., 1996, Mitochondrial nitric oxide synthase: A ubiquitous regulator of oxidative phosphorylation? Biochem. Biophys. Res. Commim. 218:40–44.

    CAS  Google Scholar 

  • Belhassen, L., Kelly, R. A., Smith, T. W., and Balligand, J. L., 1996, Nitric oxide synthase (NOS3) and contractile responsiveness to adrenergic and cholinergie agonists in the heart—Regulation of NOS3 transcription in vitro and in vivo by cyclic adenosine monophosphate in rat cardiac myocytes, J. Clin. Invest. 97:1908–1915.

    CAS  PubMed  Google Scholar 

  • Bogdan. C., Vodovotz, Y., Paik, J., Xie, Q., and Nathan, C., 1994, Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages, J. Leukocyte Biol. 55:227–233.

    CAS  PubMed  Google Scholar 

  • Bredt, D. S., 1996, Targeting nitric oxide to its targets, Proc. Soc. Exp. Biol. Med. 211:41–48.

    CAS  PubMed  Google Scholar 

  • Bredt, D. S., and Snyder, S. H., 1989. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum, Proc. Natl. Acad. Sci. USA 86:9030–9033.

    CAS  PubMed  Google Scholar 

  • Bredt, D. S., and Snyder, S. H., 1990, Isolation of nitric oxide synthase, a calmodulin-requiring enzyme, Proc. Natl. Acad. Sci. USA 87:682–685.

    CAS  PubMed  Google Scholar 

  • Bredt, D. S., Ferris, C. D., and Snyder, S. H., 1992, Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites, J. Biol. Chem. 267:10976–10981.

    CAS  PubMed  Google Scholar 

  • Bredt, D. S., Hwang, P. M., Glatt, C. E., Lowenstein, C., Reed, R. R., and Snyder, S. H., 1991, Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase, Nature 351:714–718.

    Article  CAS  PubMed  Google Scholar 

  • Brenman, J. E., Chao, D. S., Gee, S. H., McGee, A. W., Craven, S. E., Santillano, D. R., Wu, Z. Q., Huang, F., Xia, H. H., Peters, M. F., Froehner, S. C., and Bredt, D. S., 1996, Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains, Cell 84:757–767.

    Article  CAS  PubMed  Google Scholar 

  • Buga, G. M., Griscavage, J. M., Rogers, N. E., and Ignarro, L. J., 1993, Negative feedback regulation of endothelial cell function by nitric oxide, Circ. Res. 73:808–812.

    CAS  PubMed  Google Scholar 

  • Cattell, V., and Jansen, A., 1995, Inducible nitric oxide synthase in inflammation, Histochem. J. 27:777–784.

    Article  CAS  PubMed  Google Scholar 

  • Chandler, L. J., Kopnisky, K., Richards, E., Crews, F. T., and Sumners, C., 1995, Angiotensin II decreases inducible nitric oxide synthase expression in rat astroglial cultures, Am. J. Physiol. Cell. Physiol. 37:C700–C707.

    Google Scholar 

  • Chartrain, N. A., Geller, D. A., Koty, P. P., Sitrin, N. F., Nussler, A. K., Hoffman, E. P., Billiar, T. R., Hutchinson, N. I., and Mudgett, J. S., 1994, Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene, J. Biol. Chem. 269:6765–6772.

    CAS  PubMed  Google Scholar 

  • Chen, P. F., Tsai, A. L., Berka, V., and Wu, K. K., 1996, Endothelial nitric-oxide synthase—Evidence for bidomain structure and successful reconstitution of catalytic activity from two separate domains generated by a baculovirus expression system, J. Biol. Chem. 271:14631–14635.

    CAS  PubMed  Google Scholar 

  • Chen, P. Y., and Sanders, P. W., 1993, Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats, Hypertension 22:812–818.

    CAS  PubMed  Google Scholar 

  • Cho, H. J., Martin, E., Xie, Q. W., Sassa, S., and Nathan, C., 1995, Inducible nitric oxide synthase: Identification of amino acid residues essential for dimerization and binding of tetrahydrobiopterin, Proc. Natl. Acad. Sci. USA 92:11514–11518.

    CAS  PubMed  Google Scholar 

  • Chung, E., Curtis, D., Chen, G., Marsden, P. A., Twells, R., Xu, W. M., and Gardiner, M., 1996, Genetic evidence for the neuronal nitric oxide synthase gene (NOS1) as a susceptibility locus for infantile pyloric stenosis, Am. J. Hum. Genet. 58:363–370.

    CAS  PubMed  Google Scholar 

  • Colasanti, M., Persichini, T., Menegazzi, M., Mariotto, S., Giordano, E., Caldarera, C. M., Sogos, V., Lauro, G. M., and Suzuki, H., 1995, Induction of nitric oxide synthase mRNA expression—Suppression by exogenous nitric oxide, J. Biol. Chem. 270:26731–26733.

    CAS  PubMed  Google Scholar 

  • Corbelt, J. A., Kwon, G., Marino, M. H., Rodi, C. P., Sullivan, P. M., Turk, J., and McDaniel, M. L., 1996, Tyrosine kinase inhibitors prevent cylokine-induced expression of iNOS and COX-2 by human islets, Am. J. Physiol. Cell. Physiol. 39:C1581–C1587.

    Google Scholar 

  • Cross, A. H., Misko, T. P., Lin, R. F., Hickey, W. F., Trotter, J. L., and Tilton, R. G., 1994, Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice, J. Clin. Invest. 93:2684–2690.

    CAS  PubMed  Google Scholar 

  • Davda, R. K., Chandler, L. J., Crews, F. T., and Guzman, N. J., 1993, Ethanol enhances the endothelial nitric oxide synthasu response to agonists, Hypertension 21:939–943.

    CAS  PubMed  Google Scholar 

  • Davda, R. K., Chandler, L. J., and Guzman, N. J., 1994, Protein kinase C modulates receptor-independent activation of endothelial nitric oxide synthase, Eur. J. Pharmacol. Mol. Pharmucol. 266:237–244.

    CAS  Google Scholar 

  • Dawson, T. M, and Dawson, V. L., 1996, Nitric oxide synthase: Role as a transmitter/mediator in the brain and endocrine system, Annu. Rev. Med. 47:219–227.

    CAS  PubMed  Google Scholar 

  • Dawson, V. L., and Dawson, T. M., 1996a, Nitric oxide actions in neurochemistry, Neurochem. Int. 29:97–110.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Deng, A. Y., and Rapp, J. P., 1995, Locus for the inducible, but not a constitutive, nitric oxide synthase cosegregates with blood pressure in the Dahl salt-sensitive rat, J. Clin. Invest. 95:2170–2177.

    CAS  PubMed  Google Scholar 

  • Deng, A. Y, Rapp, J. P., Kato, H., and Bihoreau, M. T., 1995, Linkage mapping of the neuronal nitric oxide synthase gene (Nos1) to rat chromosome 12, Mamm. Genome 6:824.

    CAS  PubMed  Google Scholar 

  • Devera, M. E., Shapiro, R. A., Nussler, A. K., Mudgett, J. S., Simmons, R. L., Morris, S. M., Billiar, T. R., and Geller, D. A., 1996, Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: Initial analysis of the human NOS2 promoter, Proc. Natl. Acad. Sci. USA 93:1054–1059.

    CAS  Google Scholar 

  • Dinerman, J. L., Dawson, T. M., Schell, M. J., Snowman, A., and Snyder, S. H., 1994, Endothelial nitric oxide synthase localized to hippocampal pyramidal cells: Implications for synaptic plasticity, Proc. Natl. Acad. Sci. USA 91:4214–4218.

    CAS  PubMed  Google Scholar 

  • Ding, A. H., Nathan, C. F., and Stuehr, D. J., 1988, Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages, J. Immunol. 141:2407–2412.

    CAS  PubMed  Google Scholar 

  • Dong, Z., Qi, X., Xie, K., and Fidler, I. J., 1993, Protein tyrosinc kinase inhibitors decrease induction of nitric oxide synthase activity in lipopolysaccharide-responsive and lipopolysaccharide-nonresponsive murine macrophages, J. Immunol. 151:2717–2724.

    CAS  PubMed  Google Scholar 

  • Doyle, C., Holscher, C., Rowan, M. J., and Anwyl, R., 1996, The selective neuronal NO synthase inhibitor 7-nitro-indazole blocks both long-term potentiation and depotentiation of field EPSPs in rat hippocampal CA1 in vivo, J. Neurosci. 16:418–424.

    CAS  PubMed  Google Scholar 

  • Durante, W., Liao, L., Iftikhar, I., O’Brien, W. E., and Schafer, A. I., 1996, Differential regulation of l-arginine transport and nitric oxide production by vascular smooth muscle and endothelium, Circ. Res. 78:1075–1082.

    CAS  PubMed  Google Scholar 

  • Eason, S., and Martin, W., 1995, Involvement of tyrosine kinase and protein kinase C in the induction of nitric oxide synthase by lipopolysaccharide and interferon-gamma in J774 macrophages, Arch. Int. Pharmacodyn. Ther. 330:225–240.

    CAS  PubMed  Google Scholar 

  • Farivar, R. S., Chobanian, A. V., and Brecher, P., 1996, Salicylate or aspirin inhibits the induction of the inducible nitric oxide synthase in rat cardiac fibroblasts, Circ. Res. 78:759–768.

    CAS  PubMed  Google Scholar 

  • Feinstein, D. L., Galea, E., Cermak, J., Chugh, P., Lyandvert, L., and Reis, D. J., 1994, Nitric oxide synthase expression in glial cells: Suppression by tyrosine kinase inhibitors, J. Neurochem. 62:811–814.

    CAS  PubMed  Google Scholar 

  • Flodstrom, M., Welsh, N., and Eizirik, D. L., 1996, Cytokines activate the nuclear factor kappa B (NF-kappa B) and induce nitric oxide production in human pancreatic islets, FEBS Lett. 385:4–6.

    CAS  PubMed  Google Scholar 

  • Forstermann, U., Oath, I., Schwarz, P., Closs, E. I., and Kleinert, H., 1995a, Isoforms of nitric oxide synthase—Properties, cellular distribution and expressional control, Biochem. Pharmacol. 50:1321–1332.

    Article  CAS  PubMed  Google Scholar 

  • Forstermann, U., Kleinert, H., Gath, I., Schwarz, P., Closs, E. I., and Dun, N.J., 1995b, Expression and expressional control of nitric oxide synthases in various cell types, in Nitric Oxide (L. Ignarro and F. Murad, eds.) pp. 171–186, San Diego, Academic Press.

    Google Scholar 

  • Frey, C., Narayanan, K., McMillan, K., Spack, L., Gross, S. S., Masters, B. S., and Griffith, O. W., 1994, l-Thiocitrtilline—astereospecific, heme-bindinginhibitor of nitric-oxidesynthases, J. Biol.Chem. 269:26083–26091.

    CAS  PubMed  Google Scholar 

  • Fukuto, J. M., and Chaudhuri, G., 1995, Inhibition of constitutive and inducible nitric oxide synthase: Potential selective inhibition, Annu. Rev. Pharmucol. Taxicol. 35:165–194.

    CAS  Google Scholar 

  • Furfine, K. S., Harmon, M. F., Paith, J. E., Knowles, R. G., Sailer, M., Kiff, R. J., Duffy, C., Hazelwood, R., Oplinger, J. A., and Garvey, E. P., 1994, Potent and selective inhibition of human nitric oxide synthases— Selective inhibition of neuronal nitric oxide synthase by S-methyl-l-thiocitrulline and S-ethyl-l-thiocitrulline, J. Biol. Chem. 269:26677–26683.

    CAS  PubMed  Google Scholar 

  • Garciacardena, G., Oh, P., Liu, J. W., Schnitzer, J. E., and Sessa, W. C., 1996, Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: Implications for nitric oxide signaling, Proc. Natl. Acad. Sci. USA 93:6448–6453.

    CAS  Google Scholar 

  • Garvey, E. P., Oplinger, J. A., Tanoury, G. J., Sherman, P. A., Fowler, M, Marshall, S., Harmon, M. F., Paith, J. E., and Furfine, E. S., 1994, Potent and selective inhibition of human nitric oxide synthases—inhibition by non-amino acid isothioureas, J. Biol. Chem. 269:26669–26676.

    CAS  PubMed  Google Scholar 

  • Geng, Y., Maier, R., and Lotz, M., 1995, Tyrosine kinases are involved with the expression of inducible nitric oxide synthase in human articular chondrocytes, J. Cell. Physiol. 163:545–554.

    Article  CAS  PubMed  Google Scholar 

  • Ghosh, D. K., Abusoud, H. M., and Stuehr, D. J., 1996, Domains of macrophage NO synthase have divergent roles in forming and stabilizing the active dimeric enzyme, Biochemistry 35:1444–1449.

    CAS  PubMed  Google Scholar 

  • Gill, D. J., Low, B. C., and Grigor, M. R., 1996, Interleukin-1 beta and tumor necrosis factor-alpha stimulate the cat-2 gene of theL-arginine transporter in cultured vascular smooth muscle cells, J. Biol. Chem. 271:11280–11283.

    CAS  PubMed  Google Scholar 

  • Griffiths, M. J. D., Messent, M., Curzen, N. P., and Evans, T. W., 1995, Aminoguanidine selectively decreases cyclic CMP levels produced by inducible nitric oxide synthase, Am. J. Respir. Crit. Care Med. 152:1599–1604.

    CAS  PubMed  Google Scholar 

  • Griscavage, J. M., Wilk, S., and Ignarro, L. J., 1996, Inhibitors of the proteasome pathway interfere with induction of nitric oxide synthase in macrophages by blocking activation of transcription factor NF-kappa B, Proc. Natl. Acad. Sci. USA 93:3308–3312.

    Article  CAS  PubMed  Google Scholar 

  • Gross, S. S., and Levi, R., 1992, Tetrahydrobiopterin synthesis: An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle, J. Biol. Chem. 267:25722–25729.

    CAS  PubMed  Google Scholar 

  • Grozdanovic, Z., Gosztonyi, G., and Gossrau, R., 1996, Nitric oxidesynthase I (NOS-I) is deficient in the sarcolemma of striated muscle fibers in patients with Duchenne muscular dystrophy, suggesting an association with dystrophin, Acta Histochem. 98:61–69.

    CAS  PubMed  Google Scholar 

  • Hecker, M., Preiss, C., Schinikerth, V. B., and Busse, R., 1996, Antioxidants differentially affect nuclear factor kappa B-mediated nitric oxide synthase expression in vascular smooth muscle cells, FEBS Lett. 380:224–228.

    Article  CAS  PubMed  Google Scholar 

  • Hevel, J. M., and Marletta, M. A., 1994, Nitric-oxide synthase assays, in Methods Enzymol. 233:250–258.

    CAS  PubMed  Google Scholar 

  • Hirsch, D. B., Steiner, J. P., Dawson, T. M., Mammen, A., Hayek, E., and Snyder, S. H., 1993, Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes, Curr. Biol. 3:749–754.

    Article  CAS  PubMed  Google Scholar 

  • Huang, P. L., Dawson, T. M., Bredt, D. S., Snyder, S. H., and Fishman, M. C., 1993, Targeted disruption of the neuronal nitric oxide synthase gene, Cell 75:1273–1286.

    CAS  PubMed  Google Scholar 

  • Huang, Z. H., Huang, P. L., Panahian, N., Dalkara, T., Fishman, M. C., and Moskowitz, M. A., 1994, Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase, Science 265:1883–1885.

    CAS  PubMed  Google Scholar 

  • Hunot, S., Boissiere, K, Faucheux, B., Brugg, B., Mouattprigent, A., Agid, Y., and Hirsch, E. C., 1996, Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease, Neuroscience 72:355–363.

    Article  CAS  PubMed  Google Scholar 

  • Ikeda, U., Maeda, Y, Kawahara, Y, Yokoyama, M., and Shimada, K., 1995, Angiotensin II augments cytokine-stimulated nitric oxide synthesis in rat cardiac myocytes, Circulation 92:2683–2689.

    CAS  PubMed  Google Scholar 

  • Jaffrey, S. R., and Snyder, S. H., 1995, Nitricoxide: A neural messenger, Annu. Rev. Cell. Dev. Biol. 11:417–440.

    Article  CAS  PubMed  Google Scholar 

  • Joly, G. A., Narayanan, K., Griffith, O. W., and Kilbourn, R. G., 1995, Characterization of the effects of two new arginine/citrulline analogues on constitutive and inducible nitric oxide synthases in rat aorta, Br. J. Pharmacol. 115:491–497.

    CAS  PubMed  Google Scholar 

  • Kadowaki, K., Kishimoto, J., Leng, G., and Emson, P. C., 1994, Up-regulation of nitric oxide synthase (Nos) gene expression together with Nos activity in the rat hypothalamo-hypophysial system after chronic salt loading—evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion, Endocrinology 134:1011–1017.

    Article  CAS  PubMed  Google Scholar 

  • Kiechte, F. L., and Malinski, T., 1993, Nitric oxide: Biochemistry, pathophysiology, and detection, Am. J. Clin. Pathol. 100:567–575.

    Google Scholar 

  • Klatt, P., Pfeiffer, S., List, B. M., Lehner, D., Glatter, O., Bachinger, H. P., Werner, E. R., Schmidt, K., and Mayer, B., 1996, Characterization of heme-deficient neuronal nitric-oxide synthase reveals a role for heme in subunit dimerization and binding of the amino acid substrate and tetrahydrobiopterin, J. Biol. Chem. 271:7336–7342.

    CAS  PubMed  Google Scholar 

  • Kleinert, H., Euchenhofer, C., Ihrigbiedert, I., and Forstermann, U., 1996a, Glucocorticoids inhibit the induction of nitric oxide synthase II by down-regulating cytokine-induced activity of transcription factor nuclear factor-kappa B, Mol. Pharmacol. 49:15–21.

    CAS  PubMed  Google Scholar 

  • Kleinert, H., Euchenhofer, C., Ihrigbiedert, I., and Forstermann, U., 1996b, In murine 3T3 fibroblasts, different second messenger pathways resulting in the induction of NO synthase II (iNOS) converge in the activation of transcription factor NF-kappa B, J. Biol. Chem. 271:6039–6044.

    CAS  PubMed  Google Scholar 

  • Knowles, R. G., and Moncada, S., 1994, Nitric oxide synthascs in mammals, Biochem. J. 298:249–258.

    CAS  PubMed  Google Scholar 

  • Kobzik, L., Stringer, B., Balligand, J. L., Reid, M. B., and Stamler, J. S., 1995, Endothelial-type nitric oxide synthase in skeletal muscle fibers: Mitochondrial relationships, Biochem. Biophys. Res. Commun. 211:375–381.

    Article  CAS  PubMed  Google Scholar 

  • Kopp, E., and Ghosh, S., 1994, Inhibition of NF-kappa B by sodium salicylate and aspirin, Science 265:956–959.

    CAS  PubMed  Google Scholar 

  • Laubach, V. E., Shesely, E. G., Smithies, O., and Sherman, P. A., 1995, Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death, Proc. Natl. Acad. Sci. USA 92:10688–10692.

    CAS  PubMed  Google Scholar 

  • Lowe, P. N., Smith, D., Stammers, D. K., Riverosmoreno, V., Moncada, S., Charles, I., and Boyhan, A., 1996, Identification of the domains of neuronal nitric oxide synthase by limited proteolysis, Biochem. J. 314:55–62.

    CAS  PubMed  Google Scholar 

  • Lowenstein, C. J., Alley, E. W., Raval, P., Snowman, A. M., Snyder, S. H., Russell, S. W., and Murphy, W. J., 1993, Macrophage nitric oxide synthase gene—Two upstream regions mediate induction by interfcrongamma and lipopolysaccharide, Proc. Natl. Acad. Sci. USA 90:9730–9734.

    CAS  PubMed  Google Scholar 

  • Lowenstein, C. J., Dinerman, J. L., and Snyder, S. H., 1994, Nitric oxide—A physiologic messenger, Ann. Intern. Med. 120:227–237.

    CAS  PubMed  Google Scholar 

  • Macmicking, J. D., Nathan, C., Hom, G., Chartrain, N., Fletcher, D. S., Trumbauer, M., Stevens, K., Xie, Q. W., Sokol, K., Hutchinson, N., Chen, H., and Mudgett, J. S., 1995, Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81:641–650.

    Article  CAS  PubMed  Google Scholar 

  • Marletta, M. A., 1993, Nitric oxide synthase: Function and mechanism, Adv. Exp. Med. Biol. 338:281–284.

    CAS  PubMed  Google Scholar 

  • Marletta, M. A., 1994a, Approaches toward selective inhibition of nitric oxide synthase, J. Med. Chem. 37:1899–1907.

    Article  CAS  PubMed  Google Scholar 

  • Marletta, M. A., 1994b, Nitric oxide synthase: Aspects concerning structure and catalysis, Cell 78:927–930.

    Article  CAS  PubMed  Google Scholar 

  • Marsden, P. A., Heng, H., Duff, C. L., Shi, X. M., Tsui, L. C., and Hall, A. V., 1994, Localization of the human gene for inducible nitric oxide synthase (NOS2) to chromosome I7q l1.2-ql2, Genomics 19:183–185.

    Article  CAS  PubMed  Google Scholar 

  • Masada, M., Matsumoto, J., and Akino, M., 1990, Biosynthetic pathways of pteridines and their association with phenotypic expression in vitro in normal and neoplastic pigment cells from goldfish, Pigment Cell Res. 3:61–70.

    CAS  PubMed  Google Scholar 

  • Mayer, B., Klatt, P., Werner, E. R., and Schmidt, K., 1994, Molecular mechanisms of inhibition of porcine brain nitric oxide synthase by the antinociceptive drug 7-nitro-indazole, Neuropharmacology 33:1253–1259.

    CAS  PubMed  Google Scholar 

  • Michel, T., Li, G. K., and Busconi, L., 1993, Phosphorylation and subcellular translocation of endothelial nitric oxide synthase, Proc. Natl. Acad. Sci. USA 90:6252–6256.

    CAS  PubMed  Google Scholar 

  • Mitchell, H. H., Shonle, H. A., and Grindley, H. S., 1916, The origin of nitrate in the urine, J. Biol. Chem. 24:461.

    CAS  Google Scholar 

  • Moncada, S., Palmer, R. M. J., and Higgs, E. A., 1991, Nitric oxide: Physiology,pathophysiology and pharmacology, Pharmacol. Rev. 43:109–142.

    CAS  PubMed  Google Scholar 

  • Moore, P. K., Wallace, P., Gaffen, Z., Hart, S. L., and Babbedge, R. C., 1993, Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: Antinociceptive and cardiovascular effects, Dr. J. Pharmacol. 110:219–224.

    CAS  Google Scholar 

  • Moore, W. M., Webber, R. K., Jerome, G. M., Tjoeng, F. S., Misko, T. P., and Currie, M. G., 1994, L-N-6-(l-iminoethyl)lysine: A selective inhibitor of inducible nitric oxide synthase, J. Med. Chem. 37:3886–3888.

    Article  CAS  PubMed  Google Scholar 

  • Muller, J. M., Ziegler-Heitbrock, H. W., and Baeuerle, P. A., 1993, Nuclear factor kappa B, a mediator of lipopolysaccharide effects, Immunobiology 187:233–256.

    CAS  PubMed  Google Scholar 

  • Myatt, L., Brockman, D. E., Eis, A., and Pollock, J. S., 1993a, Immunohistochemical localization of nitric oxide synthase in the human placenta, Placenta 14:487–495.

    CAS  PubMed  Google Scholar 

  • Myatt, L., Brockman, D. E., Langdon, G., and Pollock, J. S., 1993b, Constitutive calcium-dependent isoform of nitric oxide synthase in the human placental villous vascular tree, Placenta 14:373–383.

    CAS  PubMed  Google Scholar 

  • Nakane, M., Klinghofer, V., Kuk, J. E., Donnelly, J. L., Budzik, G. P., Pollock, J. S., Basha, F., and Carter, G. W., 1995, Novel potent and selective inhibitors of inducible nitric oxide synthase, Mol. Pharmacol. 47:831–834.

    CAS  PubMed  Google Scholar 

  • Nakayama, I., Kawahara, Y., Tsuda, T., Okuda, M., and Yokoyama, M., 1994, Angiotensin-II inhibits cytokine-stimulated induciblc nitric oxide synthase expression in vascular smooth muscle cells, J. Biol. Chem. 269:11628–11633.

    CAS  PubMed  Google Scholar 

  • Narayanan, K., and Griffith, O. W.,1994, Synthesis of l-thiocitrulline, l-homothiocitrulline, and S-methyl-l-thiocitrulline—A new class of potent nitric oxide synthase inhibitors, J. Med. Chem. 37:885–887.

    Google Scholar 

  • Narayanan, K., Spack, L., McMillan, K., Kilbourn, R. G., Hayward, M. A., Masters, B. S. S., and Griffith, O. W., 1995, S-alkyl-L-thiocitrullines—Potent stereoselective inhibitors of nitric oxide synthase with strong pressor activity in vivo, J. Biol. Chem. 270:11103–11110.

    Article  CAS  PubMed  Google Scholar 

  • Nathan, C., and Xie, Q. W., 1994a, Nitric oxide synthases: Roles, tolls, and controls, Cell 78:915–918.

    Article  CAS  PubMed  Google Scholar 

  • Nathan, C., and Xie, Q. W., 1994b, Regulation of biosynthesis of nitric oxide, J. Biol. Chem. 269:13725–13728.

    CAS  PubMed  Google Scholar 

  • Nelson, R. J., Demas, O. E., Huang, P. L., Fishman, M. C., Dawson, V. L., Dawson, T. M., and Snyder, S. H., 1995, Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase, Nature 378:383–386.

    CAS  PubMed  Google Scholar 

  • Noris, M., Morigi, M., Donadelli, R., Aiello, S., Foppolo, M., Todeschini, M., Orisio, S., Remuzzi, G., and Remuzzi, A., 1995, Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions, Circ: Res. 76:536–543.

    CAS  Google Scholar 

  • North, A. J., Star, R. A., Brannon, T. S., Ujiie, K., Wells, L. B., Lowenstein, C. J., Snyder, S. H., and Shaul, P. W., 1994, Nitric oxide synthase type I and type I I I gene expression are developmentally regulated in rat lung, Am. J. Physiol. 266:L635–L641.

    CAS  Google Scholar 

  • Nussler, A. K., and Billiar, T. R., 1993, Inflammation, immunoregulation and inducible nitric oxide synthase, J. Leukocyte Biol. 54:171–178.

    CAS  PubMed  Google Scholar 

  • Palombella, V. J., Rando, O. J., Goldberg, A. L., and Maniatis, T., 1994, The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B, Cell 78:773–785.

    Article  CAS  PubMed  Google Scholar 

  • Peng, H. B., Libby, P., and Liao, J. K., 1995, Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa b, J. Biol. Chem. 270:14214–14219.

    CAS  PubMed  Google Scholar 

  • Pollock, J. S., Nakane, M., Buttery, L., Martinez, A., Springall, D., Polak, J. M., Förstermann, U., and Murad, F., 1993, Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies, Am. J. Physiol. Cell. Physiol. 265:C1379–C1387.

    CAS  Google Scholar 

  • Raij, L., 1994, Glomerular thrombosis in pregnancy: Role of the l-arginine-nitric oxide pathway, Kidney Int. 45:775–781.

    CAS  PubMed  Google Scholar 

  • Reid, M. B., 1996, Reactive oxygen and nitric oxide in skeletal muscle, News Physiol. Sci. 11:114–119.

    CAS  Google Scholar 

  • Robinson, L. J., and Michel, T., 1995, Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting, Proc. Natl. Acad. Sci. USA 92:11776–11780.

    CAS  PubMed  Google Scholar 

  • Robinson, L. J., Weremowicz, S., Morton, C. C., and Michel, T., 1994, Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene, Genomics 19:350–357.

    Article  CAS  PubMed  Google Scholar 

  • Robinson, L. J., Busconi, L., and Michel, T., 1995, Agonist-modulated palmitoylation of endothelial nitric oxide synthase, J. Biol. Chem. 270:995–998.

    Article  CAS  PubMed  Google Scholar 

  • Scheinman, R. I., Cogswell, P. C., Lofquist, A. K., and Baldwin, A. S., Jr., 1995, Role of transcriptional activation of IκBα in mediation of immunosuppression by glucocorticoids, Science 270:283–286.

    CAS  PubMed  Google Scholar 

  • Schmidt, H. H. H. W., Pollock, J. S., Nakane, M., Gorsky, L. D., Förstermann, U., and Murad, F., 1991, Purification of a soluble isoform of guanylyl cyclase-activating factor synthase, Proc. Natl. Acad. Sci. USA 88:365–369.

    CAS  PubMed  Google Scholar 

  • Sennequier, N., and Stuehr, D. J., 1996, Analysis of substrate-induced electronic, catalytic, and structural changes in inducible NO synthase, Biochemistry 35:5883–5892.

    Article  CAS  PubMed  Google Scholar 

  • Seo, H. G., Fujiwara, N., Kaneto, H., Asahi, M., Fujii, J., and Taniguchi, N., 1996, Effect of a nitric oxide synthase inhibitor, S-ethylisothiourea, on cultured cells and cardiovascular functions of normal and lipopolysaccharide-treated rabbits, J. Biochem. 119:553–558.

    CAS  PubMed  Google Scholar 

  • Sessa, W. C., Barber, C. M., and Lynch, K. R., 1993, Mutation of N-myrisloylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein, Circ. Res. 72:921–924.

    CAS  PubMed  Google Scholar 

  • Sessa, W. C., Pritchard, K., Seyedi, N., Wang, J., and Hintze, T. H., 1994, Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression, Circ. Res. 74:349–353.

    CAS  PubMed  Google Scholar 

  • Shultz, P. J., and Raij, L., 1992, Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis, J. Clin. Invest. 90:1718–1725.

    CAS  PubMed  Google Scholar 

  • Siddhanta, U., Wu, C. Q., Abusoud, H. M., Zhang, J. L., Ghosh, D. K., and Stuehr, D. J., 1996, Heme iron reduction and catalysis by a nitric oxide synthase heterodimer containing one reductase and two oxygenase domains, J. Biol. Chem. 271:7309–7312.

    CAS  PubMed  Google Scholar 

  • Singh, K., Balligand, J. L., Fischer. T. A., Smith, T. W., and Kelly, R. A., 1996, Regulation of cytokine-inducible nitric oxide synthase in cardiac myocytes and microvascular endothelial cells—Role of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and STAT1 alpha, J. Biol. Chem. 271:1111–1117.

    CAS  PubMed  Google Scholar 

  • Southan, G. J., and Szabo, C., 1996, Selective pharmacological inhibition of distinct nitric oxide synthase isoforms, Biochem. Pharmacol. 51:383–394.

    Article  CAS  PubMed  Google Scholar 

  • Southan, G. J., Szabo, C., O’Connor, M. P., Salzman, A. L., and Thiemermann, C., 1995a, Amidines are potent inhibitors of nitric oxide synthases: Preferential inhibition of the inducible isoform, Eur. J. Pharmacol. Mol. Pharm. 291:311–318.

    CAS  Google Scholar 

  • Southan, G. J., Szabo, C., and Thiemermann, C., 1995b, Isothioureas: Potent inhibitors of nitric oxide synthases with variable isoform selectivity, Br. J. Pharmacol. 114:510–516.

    CAS  PubMed  Google Scholar 

  • Spink, J., Cohen, J., and Evans, T. J., 1995, The cytokine responsive vascular smooth muscle cell enhancer of inducible nitric oxide synthase—Activation by nuclear factor-kappa B, J. Biol. Chem. 270:29541–29547.

    CAS  PubMed  Google Scholar 

  • Stuehr, D. J., and Griffith, O. W., 1992, Mammalian nitric oxide synthases, Adv. Enzymol. 65:287–346.

    CAS  PubMed  Google Scholar 

  • Su, Z. Z., Blazing, M. A., Fan, D., and George, S. E., 1995, The calmodulin-nitric oxide synthase interaction—Critical role of the calmodulin latch domain in enzyme activation, J. Biol. Chem. 270:29117–29122.

    Article  CAS  PubMed  Google Scholar 

  • Szabo, C., Southan, G. J., and Thiemermann, C., 1994, Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase, Proc. Natl. Acad. Sci. USA 91:12472–12476.

    CAS  PubMed  Google Scholar 

  • Tetsuka. T., Baier, L. D., and Morrison, A. R., 1996, Antioxidants inhibit interleukin-1-induced cyclooxygenase and nitric-oxide synthase expression in rat mesangial cells—Evidence for post-transcriptional regulation, J. Biol. Chem. 271:11689–11693.

    Article  CAS  PubMed  Google Scholar 

  • Tomimoto, H., Akiguchi, I., Wakita, H., Nakamura, S., and Kimura, J., 1994, Histochemical demonstration of membranous localization of endothelial nitric oxide synthase in endothelial cells of the rat brain, Brain Res. 667:107–110.

    Article  CAS  PubMed  Google Scholar 

  • Tracey, W. R., Pollock, J. S., Murad, F., Nakane, M., and Forstermann, U., 1994, Identification of an endothelial-like type III NO synthase in LLC-PK1 kidney epithelial cells, Am. J. Physiol. 266:C22–C28.

    CAS  PubMed  Google Scholar 

  • Vanderwinden, J. M., De, L. M., Schiffmann, S. N., Mailleux, P., Lowenstein, C. J., Snyder, S. H., and Vanderhaeghen, J. J., 1993, Nitric oxide synthase distribution in the enteric nervous system of Hirschsprung’s disease, Gastroenterology 105:969–973.

    CAS  PubMed  Google Scholar 

  • Venema, R. C., Sayegh, H. S., Kent, J. D., and Harrison, D. G., 1996, Identification, characterization, and comparison of the calmodulin-binding domains of the endothelial and inducible nitric oxide synthases, J. Biol. Chem. 271:6435–6440.

    CAS  PubMed  Google Scholar 

  • Vodovolz, Y., Bogdan, C., Paik, J., Xie, Q.-W., and Nathan, C., 1993, Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor-β, J. Exp. Med. 178:605–613.

    Google Scholar 

  • Wei, X. Q., Charles, I. G., Smith, A., Ure, J., Feng, C. J., Huang, F. P., Xu, D. M., Muller, W., Moncada, S., and Liew, F. Y., 1995, Altered immune responses in mice lacking inducible nitric oxide synthase, Nature 375:408–411.

    Article  CAS  PubMed  Google Scholar 

  • Weigert, A. L., Higa, E. M. S., Niederberger, M., McMurtry, I. F, Raynolds, M., and Schrier, R. W., 1995, Expression and preferential inhibition of inducible nitric oxide synthase in aortas of endotoxemic rats, J. Am. Soc. Nephrol. 5:2067–2072.

    CAS  PubMed  Google Scholar 

  • Weiner, C. P., Lizasoain, I., Baylis, S. A., Knowles, R. G., Charles, I. G., and Moncada, S., 1994, Induction of calcium-dependent nitric oxide synthases by sex hormones, Proc. Natl. Acad. Sci. USA 91:5212–5216.

    CAS  PubMed  Google Scholar 

  • Weisz, A., Oguchi, S., Cicatiello, L., and Esumi, H., 1994, Dual mechanism for the control of inducible-type NO synthase gene expression in macrophages during activation by interferon-gamma and bacterial lipopolysacchande—Transcriptional and post-transcriptional regulation, J. Biol. Chem. 269:8324–8333.

    CAS  PubMed  Google Scholar 

  • Xie, Q. W., and Nathan, C., 1994, The high-output nitric oxide pathway: role and regulation, J. Leukocyte. Biol. 56:576–582.

    CAS  PubMed  Google Scholar 

  • Xie, Q., Cho, H. J., Calaycay, J., Mumford, R. A., Swiderek, K. M., Lee, T. D., Ding, A., Troso, T., and Nathan, C., 1992, Cloning and characterization of inducible nitric oxide synthase from mouse macrophages, Science 256:225–228.

    CAS  PubMed  Google Scholar 

  • Xie, Q., Whisnant, R., and Nathan, C., 1993, Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon-γ and bacterial lipopolysaccharide, J. Exp. Med. 177:1779–1784.

    Article  CAS  PubMed  Google Scholar 

  • Xie, Q., Kashiwabara, Y., and Nathan, C., 1994, Role of transcription factor NF-κB/Rc in the induction of nitric oxide synthase, J. Biol. Chem. 269:4705–4708.

    CAS  PubMed  Google Scholar 

  • Xue, C., Pollock, J., Schmidt, H. H. H. W., Ward, S. M., and Sanders, K. M., 1994, Expression of nitric oxide synthase immunoreactivity by interstitial cells of the canine proximal colon, J. Auton. Nerv. Syst. 49:1–14.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto, R., Bredt, D. S., Snyder, S. H., and Stone, R. A., 1993, The localization of nitric oxide synthase in the rat eye and related cranial ganglia, Neuroscience 54:189–200.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida, K., Okamura, T., Kimura, H., Bredt, D. S., Snyder, S. H., and Toda, N., 1993, Nitric oxide synthase-immunoreactive nerve fibers in dog cerebral and peripheral arteries, Brain Res. 629:67–72.

    Article  CAS  PubMed  Google Scholar 

  • Yoshizumi, M., Perrella, M. A., Burnett, J. C., and Lee, M., 1993, Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life, Circ. Res. 73:205–209.

    CAS  PubMed  Google Scholar 

  • Zhang, R., Min, W., and Sessa, W. C., 1995, Functional analysis of the human endothelial nitric oxide synthase promoter—SP1 and GATA factors are necessary for basal transcription in endothelial cells, J. Biol. Chem. 270:15320–15326.

    CAS  PubMed  Google Scholar 

  • Zhang, X., Verge, V., Wiesenfeld, H. Z., Ju, G., Bredt, D., Snyder, S. H., and Hökfelt, T., 1993, Nitric oxide synthase-like immunoreactivity in lumbar dorsal root ganglia and spinal cord of rat and monkey and effect of peripheral axotomy, J. Comp. Neurol. 335:563–575.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Z. G., Chopp, M., Zaloga, C., Pollock, J. S., and Forstermann, U., 1993, Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats, Stroke 24:2016–2021.

    CAS  PubMed  Google Scholar 

  • Zhang, Z.G., Chopp, M., Gautam, S., Zaloga, C., Zhang, R. L., Schmidt, H. H. H. W., Pollock, J. S., and Forstermann, U., 1994, Upregulation of neuronal nitric oxide synthase and mRNA, and selective sparing of nitric oxide synthase-containing neurons after focal cerebral ischemia in rat, Brain Res. 654:85–95.

    CAS  PubMed  Google Scholar 

  • Zoche, M., Bienert, M., Beyermann, M., and Koch, K. W., 1996, Distinct molecular recognition of calmodulin-binding sites in the neuronal and macrophage nitric oxide synthases: A surface plasmon resonance study, Biochemistry 35:8742–8747.

    Article  CAS  PubMed  Google Scholar 

  • Zweier, J. L., Kuppasamy, P., and Lutty, G. A., 1988, Measurement of endothelial cell free radical generation: Evidence for a central mechanism of free radical injury in post ischemic tissues, Proc. Natl. Acad. Sci. USA 85:4046–4056.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, D.C., 20007

    Nicolas J. Guzman & Bismark Amoah-Apraku

Authors
  1. Nicolas J. Guzman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bismark Amoah-Apraku
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic Publishers

About this chapter

Cite this chapter

Guzman, N.J., Amoah-Apraku, B. (2002). Nitric Oxide Synthase. In: Reactive Oxygen Species in Biological Systems. Springer, Boston, MA. https://doi.org/10.1007/0-306-46806-9_9

Download citation

  • DOI: https://doi.org/10.1007/0-306-46806-9_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-45756-2

  • Online ISBN: 978-0-306-46806-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation