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Role of the nitric oxide/cyclic GMP/Ca2+ signaling pathway in the pyrogenic effect of interleukin-1β

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Abstract

Interleukin-1β (IL-1β) has a wide spectrum of inflammatory, metabolic, haemopoietic, and immunological properties. Because it produces fever when injected into animals and humans, it is considered an endogenous pyrogen. There is evidence to suggest that Ca2+ plays a critical role in the central mechanisms of thermoregulation, and in the intracellular signaling pathways controlling fever induced by IL-1β and other pyrogens. Data from different labs indicate that Ca2+ and Na+ determine the temperature set point in the posterior hypothalamus (PH) of various mammals and that changes in Ca2+ and PGE2 concentrations in the cerebrospinal fluid (CSF) of these animals are associated with IL-1β-induced fever. Antipyretic drugs such as acetylsalicylic acid, dexamethasone, and lipocortin 5-(204–212) peptide counteract IL-1β-induced fever and abolish changes in Ca2+ and PGE2 concentrations in CSF. In vitro studies have established that activation of the nitric oxide (NO)/cyclic GMP (cGMP) pathway is part of the signaling cascade transducing Ca2+ mobilization in response to IL-1β and that the ryanodine (RY)- and inositol-(1,4,5)-trisphosphate (IP3)-sensitive pools are the main source of the mobilized Ca2+. It is concluded that the NO/cGMP/Ca2+ pathway is part of the signaling cascade subserving some of the multiple functions of IL-1β.

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References

  1. Feldberg W., Myers R. D., and Veale W. L. (1970) Perfusion from cerebral ventricle to cisterna magna in the unanesthetized cat. Effect of calcium on body temperature. J. Physiol. (Lond) 207, 403–416.

    CAS  Google Scholar 

  2. Myers R. D. and Veale W. L. (1971) The role of sodium and calcium ions in hypothalamus in the control of body temperature of unanesthetized cat. J. Physiol. (Lond) 212, 411–430.

    CAS  Google Scholar 

  3. Benson M. J. and Veale W. L. (1972) Thermoregulatory response to perfusing local regions of brain tissue with various ions in the conscious rabbits. Proc. Can. Fed. Biol. Soc. 15, 331.

    Google Scholar 

  4. Myers R. D. and Veale W. L. (1970) Body temperature: possible ionic mechanism in the hypothalamus controlling the set-point. Science 170, 95–97.

    PubMed  CAS  Google Scholar 

  5. Feldberg W. and Saxena P. N. (1970) Mechanism of action of pyrogen. J. Physiol. (Lond) 211, 245–261.

    CAS  Google Scholar 

  6. Myers R. D. (1982) The role of ions in thermoregulation and fever, in Handbook of Experimental Pharmacology, vol. 60 (Milton A. S., ed.), Springer-Verlag, Berlin, pp. 151–186.

    Google Scholar 

  7. Myers R. D. (1980) Hypothalamic control of thermoregulation-neurochemical mechanism, in Handbook of the Hypothalamus, vol. 3 (Morgane P. J. and Panksepp J., eds.), Maicel Dekker, New York, pp. 83–210.

    Google Scholar 

  8. Myers R. D. and Tytell M. (1972) Fever: reciprocal shift in brain sodium to calcium ratio as the set-point temperature rises. Science 178, 765–767.

    PubMed  CAS  Google Scholar 

  9. Myers (1976) Diencephalic efflux of 22Na+ and 45Ca2+ ions in the febrile cat: effect of an antipyretic. Brain Res. 103, 412–417.

    PubMed  CAS  Google Scholar 

  10. Gisolfi G., Mira F., and Myers R. D. (1977) Diencephalic efflux of calcium ions in the monkey during exercise, thermal stress and feeding. J. Physiol. (Lond.) 273, 617–630.

    CAS  Google Scholar 

  11. Watanabe H. K., Ho I. K., and Hoskins B. (1986) Effects of cold stress on brain regional calcium content in rats and mice. Brain Res. Bull. 19, 407–409.

    Google Scholar 

  12. Beleslin D. B., Rezani A. H., and Myers R. D. (1985) Divergent action of verapamil perfused in two hypothalamic areas on body temperature of the cat. Neurosci. Lett. 57, 307–312.

    PubMed  CAS  Google Scholar 

  13. Rezvani A. H., Beleslin D. B., and Myers R. D. (1986) Neuroanatomical mapping of hypothalamus regions mediating verapamil hyperthermia and hypothermia in the cat. Brain Res. Bull. 17, 249–254.

    PubMed  CAS  Google Scholar 

  14. Palmi M. and Sgaragli G. P. (1989) Hyperthermia induced in rabbits by organic calcium antagonists. Pharmacol. Biochem. Behav. 34, 325–330.

    PubMed  CAS  Google Scholar 

  15. Bernheim H. A., Gilbert T. M., and Stitt J. T. (1980) Prostaglandin E levels in third ventricular cerebrospinal fluid of rabbits during fever and changes in body temperature. J. Physiol. (Lond.) 301, 69–78.

    CAS  Google Scholar 

  16. Dinarello C. A. and Bernheim H. A. (1982) Ability of human leukocyte pyrogen to stimulate brain prostaglaindin synthesis in vitro. J. Neurochem. 37, 702–708.

    Google Scholar 

  17. Bernhaim H. A. (1986) Is Prostaglandin E2 involved in the pathogenesis of fever? Effect of Interleukin-1 on the release of prostaglandins. Yale J. Biol. Med. 59, 151–158.

    Google Scholar 

  18. Davidson J., Milton A. S., and Rotondo D. (1990) A study of the pyrogenic action of interleukin-1α and interleukin-1β: interaction with a steroidal and a non steroidal antinflammatory agent. Br. J. Pharmacol. 100, 542–546.

    PubMed  CAS  Google Scholar 

  19. Dascombe M. J. (1985) The pharmacology of fever. Prog. Neurobiol. 25, 327–373.

    PubMed  CAS  Google Scholar 

  20. Milton A. S. (1982) Prostaglandins in fever and the role of action of antipyretic drugs, in Pyretic and Antipyretic: Handbook of Experimental Pharmacology, vol. 61 (Milton A. S., ed.) Springer-Verlag, Berlin, pp. 257–303.

    Google Scholar 

  21. Palmi M., Frosini M., and Sgaragli G. P. (1992) Calcium changes in rabbit CSF during endotoxin, IL-1β and PGE2 fever. Pharmacol. Biochem. Behav. 43, 1253–1262.

    PubMed  CAS  Google Scholar 

  22. Palmi M., Frosini M., Becherucci C., Sgaragli G. P., and Parente L. (1994) Increase of extracellular brain calcium involved in interleukin-1β-induced pyresis in the rabbit: antagonism by dexamethasone. Br. J. Pharmacol. 112, 449–452.

    PubMed  CAS  Google Scholar 

  23. Milton A. S., Abul H. T., Davidson J., and Rotondo D. (1989) Antipyretic action of dexamethasone, in Thermoregulation: Research and Clinical Applications (Lomax P. and Schonbaum E., eds.), Karger, Basel, pp. 74–77.

    Google Scholar 

  24. Flower R. G. and Blackwell G. J. (1976) The importance of phospholipase A2 in prostaglandin biosynthesis. Biochem. Pharmacol. 25, 285–291.

    PubMed  CAS  Google Scholar 

  25. Marshall L. A. and Carte-Rishak M. C. (1992) Demonstration of similar calcium dependencies by mammalian light and low molecular mass phospholipase A2. Biochem. Pharmacol. 44, 1849–1858.

    PubMed  CAS  Google Scholar 

  26. Glaser K. B., Mobilio D., Chang J. Y., and Senko N. (1993) Phospholipase A2 enzymes: regulation and inhibition. Trends Pharmacol. Sci. 14, 92–98.

    PubMed  CAS  Google Scholar 

  27. Lyons-Giordano B., Davis G. L., Galbraith W., Pratta M. A., and Arner E. C. (1989) Interleukin-1β stimulates phospholipase A2 in mRNA in rabbit articular chondrocytes. Biochem. Biophys. Res. Comm. 164, 488–495.

    PubMed  CAS  Google Scholar 

  28. Pfeilschifter J., Pignat W., Vosbech K., and Marki F. (1989) Interleukin-1 and tumor necrosis factor synergistically stimulate prostaglandin synthesis and phospholipase A2 release from rat mesangial cells. Biochem. Biophys. Acta 159, 385–394.

    CAS  Google Scholar 

  29. Burch R. M., Connor J. R., and Axebrod J. (1988) Interleukin-1 amplifies receptor-mediated activation of phospholipase A2 in 3T3 fibroblasts. Proc. Natl. Acad. Sci. USA 85, 3606–3609.

    Google Scholar 

  30. Nakano T., Ohara O., Teraoka H., and Arita H. (1990) Glucocorticoids suppress group II phospholipase A2 production by blocking mRNA synthesis and post-transcriptional expression. J. Biol. Chem. 265, 12,745–12,748.

    CAS  Google Scholar 

  31. Muhl H., Geiger T., Pignat W., Marki F., Van Den Bosch H., Cerletti H., et al. (1992) Transforming growth factors type-a and dexamethasone attenuate group II phospholipase A2 gene expression by interleukin-1 and forskolin in rat mesanglial cells. FEBS Lett. 301, 190–194

    PubMed  CAS  Google Scholar 

  32. Flower R. J. (1988) Lipocortin and the mechanism of action of the glucocorticoids. Br. J. Pharmacol. 94, 987–1015.

    PubMed  CAS  Google Scholar 

  33. Solito E. and Parente L. (1989) Modulation of phospholipase A2 activity in human fibroblasts. Br. J. Pharmacol. 96, 656–660.

    PubMed  CAS  Google Scholar 

  34. Solito E., Raugel G., Melli M., and Parente L. (1991) Dexamethasone induces the expression of the mRNA of lipocortin 1 and 2 and the release of lipocortin 1 and 5 in differentiated but not undifferentiated U-937 cells. FEBS Lett. 291, 238–244.

    PubMed  CAS  Google Scholar 

  35. Davidson J., Flower R. J., Milton A. S., Peers S. H., and Rotondo D. (1991) Antipyretic action of human recombinant lipocortin-1. Br. J. Pharmacol. 102, 7–9.

    PubMed  CAS  Google Scholar 

  36. Palmi M., Frosini M., Sgaragli G. P., Becherucci C., Perretti M., and Parente L. (1995) Inhibition of interleukin-1 beta-induced pyresis in the rabbit by peptide 204–212 of lipocortin 5. Eur. J. Pharmacol. 281, 97–99.

    PubMed  CAS  Google Scholar 

  37. Palmi M., Frosini M., and Sgaragli G. P. (1996) Interleukin-1β stimulation of 45Ca2+ release from rat striatal slices. Br. J. Pharmacol. 118, 1705–1710.

    CAS  Google Scholar 

  38. Carter D. B. (1990) Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature 344, 633–640.

    PubMed  CAS  Google Scholar 

  39. Stanton T. H., Maynard M., and Bomsztyk K. (1986) Effect of Interleukin-1 on intracellular concentration of sodium, calcium and potassium in 70Z/3 cells. J. Biol. Chem. 261, 5699–5701.

    PubMed  CAS  Google Scholar 

  40. Arora P. D., Ma J., Min W., Cruz T., and McCulloch C. A. (1995) Interleukin-1-induced calcium flux in human fibroblasts is mediated through focal adhesions. J. Biol. Chem. 270, 6042–6049.

    PubMed  CAS  Google Scholar 

  41. Rambaldi A., Torcia M., Bettoni S., Borbuni T., Vannier E., Dinarello C. A., and Cozzolino F. (1990) Modulation of cell proliferation and cytokine production in acute myeloblastic leukemia by interleukin-1 receptor antagonist and lack of its expression by leukemic cells. Blood 76, 114–121.

    Google Scholar 

  42. Hannum C. H., Wilcox C. J., Areud W. P., Joslin F. G., Dripps D. J., Heimdal P. L., et al. (1990) Interleukin-1 receptor antagonist activity of human interleukin-1 inhibitor. Nature 343, 336–340.

    PubMed  CAS  Google Scholar 

  43. Dripps D. A., Verdeber E., Ray K. N. G., Thompson R. C., and Eisemberg S. P. (1991) Interleukin-1 receptor antagonist binds to the type II interleukin-1 receptor on B cells and neutrophils. J. Biol. Chem. 18, 333–364.

    Google Scholar 

  44. Arend W. P., Welgus H. G., Thompson R. C., and Eisenberg S. P. (1990) Biological properties of recombinant human monocyte-derived interleukin-1 receptor antagonist. J. Clin. Invest. 85, 1694–1697.

    PubMed  CAS  Google Scholar 

  45. Ohlsson K., Bjork P., Bergenfeldt M., Hayman R., and Thompson R. C. (1990). Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348, 550–552.

    PubMed  CAS  Google Scholar 

  46. von Uexküll C., Nourshargh S., and Williams T. J. (1992). Comparative responses of human and rabbit interleukin-1 receptor antagonists. Immunology 77, 483–487.

    Google Scholar 

  47. Coceani F., Lee J., Redford J., and Isis B. (1992). Interleukin-1 antagonist: effectiveness against interleukin-1 fever. Can J. Physiol. Pharmacol. 70, 1590–1596.

    PubMed  CAS  Google Scholar 

  48. Berridge M. J. (1993) Inositol triphosphate and calcium signalling. Nature 361, 315–324.

    PubMed  CAS  Google Scholar 

  49. Nathanson M. H., Padfield P. J., O’Sullivan A. J., Burstahler A. D., and Jamieson J. D. (1992) Mechanism of Ca2+ wave propagation in pancreatic acinar cells. J. Biol. Chem. 267, 18,118–18,121.

    CAS  Google Scholar 

  50. Friel D. D. and Tsein R. W. (1992a) A caffeine and ryanodine sensitive Ca2+ stores in bullfrog symphatetic neurones modulates effects of Ca2+ entry on [Ca2+]. J. Physiol. (Lond.) 450, 217–246.

    CAS  Google Scholar 

  51. Friel D. D. and Tsein R. W. (1992b) Phase dependent contributions from Ca2+ entry and Ca2+ release to caffeine-induced [Ca2+]i oscillations in bullfrog sympathetic neurons. Neuron 8, 1109–1125.

    PubMed  CAS  Google Scholar 

  52. Swann K. (1992) Different triggers for calcium oscillations in mouse eggs involve a ryanodine-sensitive calcium stores. Biochem. J. 287, 79–84.

    PubMed  CAS  Google Scholar 

  53. Miyaraki S. I. (1988) Inositol 1,4,5-triphosphate-induced calcium release and guanine nucleotide-binding protein-mediated periodic calcium rises in golden hamster eggs. J. Cell. Biol. 106, 345–353.

    Google Scholar 

  54. Galione A., Lee H. C., and Busa W. B. (1991) Ca2+-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science 253, 1143–1146.

    PubMed  CAS  Google Scholar 

  55. Galione A., White A., Willmott N., Turner M., Potter B. V., and Watson S. P. (1993) cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature 365, 456–459.

    PubMed  CAS  Google Scholar 

  56. Bredt D. S., Glatt C. E., Huwang P. M., Fatuhi M., Dawson T. M., and Snyder S. H. (1991) Nitric oxide synthase protein and mRNA are discretely localized in neuronal population of the mammalian CNS together with NADPH diaphorase. Neuron 7, 615–624.

    PubMed  CAS  Google Scholar 

  57. Hibbs J. R., Taintor R. R., Vaurin Z., Granger J-C., Drapier K. J., Amber K. J., and Lancaster J. R. (1990) Synthesis of nitric oxide from terminal guanidino nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron, in Nitric Oxide from L-Arginine: A Bioregulatory System (Moncada, S. and Higgs, E. A., eds.), Elsevier, New York, pp. 189–223.

    Google Scholar 

  58. Inoue T., Fukuo K., Morimoto S., Koh E., and Ogihara T. (1993) Nitric oxide mediates interleukin-1-induced prostaglandin E2 production by vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 194, 420–424

    PubMed  CAS  Google Scholar 

  59. Clementi E. (1998) Role of nitric oxide and its intracellular signalling pathways in the control of Ca2+ homeostasis. Biochem. Pharmacol. 55, 713–718.

    PubMed  CAS  Google Scholar 

  60. Leaf C. D., Wishnok J. S., Hurlry J. P., Rosenbland W. D., Fox J. G., and Tannenbaum S. R. (1990) Nitrate biosynthesis in rats, ferrets and humans. Precursor studies with L-arginine. Carcinogenesis 11, 855–858.

    PubMed  CAS  Google Scholar 

  61. Ochoa J. B., Udekwu A. O., Billiar T. R., Currand R. D., Cerra F. B., Simmons R. L., and Peitzman A. B. (1991) Nitrogen oxide levels in patients after trauma and during sepsis. Ann. Surg. 214, 621–626.

    PubMed  CAS  Google Scholar 

  62. Palmer R. M. J., Bridge L., Foxwell N. A., and Moncada S. (1992) The role of nitric oxide in endothelial cell damage and its inhibition by glucocorticoids. Br. J. Pharmacol. 105, 11–12.

    PubMed  CAS  Google Scholar 

  63. Meini A., Benocci A., Frosini M., Sgaragli G. P., Pessina P., Aldinucci C., et al. (2000) Nitric oxide modulation of interleukin-1β-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. J. Neurosci. 20, 8980–8986.

    PubMed  CAS  Google Scholar 

  64. Vincent S. R. and Johansson O. (1983) Striatal neurons containing both somatostatin and avian pancreatic polypeptide (APP) like immunoreactivities and NADPH-diaphorase activity: a light and electron microscopic study. J. Comp. Neurol. 217, 264–270

    PubMed  CAS  Google Scholar 

  65. Strijbos P. J. L. M., Leach M. J., and Garthwaite J. (1996) Vicious cycle involving Na+ channels, glutamate release, and NMDA receptors mediates delayed neurodegeneration through nitric oxide formation. J. Neurosci. 16, 5004–50013.

    PubMed  CAS  Google Scholar 

  66. Maragos C. M., Morley D., Wink D. A., Dunams T. M., Saavedra J. E., Hoffman A., et al. (1991) Complexes of •NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects. J. Med. Chem. 34, 3242–3247.

    PubMed  CAS  Google Scholar 

  67. Diodati J. G., Quyyumi A. A., Hussain N., and Keefer L. K. (1993) Complexes of nitric oxide with nucleophiles as agents for the controlled biological release of nitric oxide: antiplatelet effect. Thromb. Haemost. 70, 654–658.

    PubMed  CAS  Google Scholar 

  68. Moncada S. and Higgs A (1993) The L-arginine-nitric oxide pathway. N. Engl. J. Med. 329, 2002–2012.

    PubMed  CAS  Google Scholar 

  69. Gallo O., Masini E., Morbidelli L., Franchi A., Fini-Storchi I., Vergari W. A., and Ziche M. (1998) Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J. Natl. Cancer. Inst. 90, 587–596.

    PubMed  CAS  Google Scholar 

  70. Lowenstein C. J., Dinerman J. L., and Snyder S. H. (1994) Nitric oxide: a physiologic messenger. Ann. Intern. Med. 120, 227–237.

    PubMed  CAS  Google Scholar 

  71. Dawson V. L., Dawson T. M., Uhl G. R., and Snyder S. H. (1993) Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J. Neurosci. 13, 2651–2661.

    PubMed  CAS  Google Scholar 

  72. Dugas B., Debre P., and Moncada S. (1995) Nitric oxide, a vital poison inside the immuno and inflammatory network. Res. Immunol. 146, 664–670.

    PubMed  CAS  Google Scholar 

  73. Iadecola C. (1997) Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci. 20, 132–139.

    PubMed  CAS  Google Scholar 

  74. Kim Y. M., Bombeck C. A., and Billiar T. R. (1999) Nitric oxide as a bifunctional regulator of apoptosis. Circ. Res. 84, 253–256.

    PubMed  CAS  Google Scholar 

  75. Shimojo T., Hiroe M., and Ishiyama S. (1999) Nitric oxide induces apoptotic death in cardiomyocytes via a cyclic GMP-dependent pathway. Exp. Cell Res. 247, 38–47.

    PubMed  CAS  Google Scholar 

  76. Loweth A. C., Williams G. T., and Scarpello J. H. (1997) Evidence for the involvement of cGMP and protein kinase G in nitric oxide-induced apoptosis in pancreatic B cell line HIT-T15. FEBS Lett. 400, 285–288.

    PubMed  CAS  Google Scholar 

  77. McConkey D. J., Hartzell P., Nicotera P., and Orrenius S. (1989) Calcium-activated DNA fragmentation kills immature thymocytes. FASEB J. 7, 1843–952.

    Google Scholar 

  78. Berridge M. J., Bootman M. D., and Lipp P. (1998) Calcium-a life and death signal. Nature 395, 645–648.

    PubMed  CAS  Google Scholar 

  79. Vigne P., Feolde E., Ladoux A., Duval D., and Frelin C. (1995) Contributions of nitric oxide synthase and heme oxygenase to cyclic GMP formation by cytokine and hemin treated brain capillary endothelial cells. Biochem. Biophys. Res. Commun. 214, 1–5.

    PubMed  CAS  Google Scholar 

  80. Garthwaite J., Southam E., Boulton C. L., Nielsen E. B., Schmidt K., and Mayer B. (1995) Patent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one. Mol. Pharmacol. 48, 184–188.

    PubMed  CAS  Google Scholar 

  81. Schrammel A., Behrends S., Schmidt K., Koesling D., and Mayer B. (1996) Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase. Mol. Pharmacol. 50, 1–5.

    PubMed  CAS  Google Scholar 

  82. Mülsch A., Busse R., Lieban S., and Fimrstermann U. (1988) LY-83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase. J. Pharmacol. Exp. Ther. 247, 283–288.

    PubMed  Google Scholar 

  83. Feelisch M., Kotsonis P., Siebe J., Clement B., and Schmidt H. H. H. W. (1999) The soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one is a nonselective heme protein inhibitor of nitric oxide synthase and other cytochrome P-450 enzymes involved in nitric oxide donor bioactivation. Mol. Pharmacol. 56, 243–253.

    PubMed  CAS  Google Scholar 

  84. Brune B. Mohr S., and Messmer U. K. (1996) Protein thiol modification and apoptotic cell death as cGMP-indipendent nitric oxide (NO) signalling pathways. Rev. Physiol. Biochem. Pharmacol. 127, 1–30.

    Article  PubMed  CAS  Google Scholar 

  85. Stoyanovsky D., Murphy T., Anno P. R., Kim Y. M., and Salama G. (1997) Nitric oxide activates skeletal and cardiac ryanodine receptors. Cell Calcium 21, 19–29.

    PubMed  CAS  Google Scholar 

  86. Elliott S. J. (1996) Peroxynitrite modulates receptor-activated Ca2+ signalling in vascular endothelial cells. Am. J. Physiol. 270, L954-L961.

    PubMed  CAS  Google Scholar 

  87. Felbel J., Trockur B., Ecker T., Landgraf W., and Hofmann F. (1988) Regulation of cytosolic calcium by cAMP and cGMP in freshly isolated smooth muscle cells from bovine trachea. J. Biol. Chem. 263, 16,764–16,771.

    CAS  Google Scholar 

  88. Nguyen B. L., Saitoh M., and Ware A. (1991) Interaction of nitric oxide and cGMP with signal transduction in activated platelets. Am. J Physiol. 261, H1043-H1052.

    PubMed  CAS  Google Scholar 

  89. Clementi E., Vecchio I., Sciorati C., and Nistico G. (1995) Nitric oxide modulation of agonist-evoked intracellular Ca2+ release in neurosecretory PC-12 cells: inhibition of phospholipase C activity via cyclic GMP-dependent protein kinase 1. Mol. Pharmacol. 47, 517–524.

    PubMed  CAS  Google Scholar 

  90. Rooney T. A., Joseph S. K., Queen C., and Thomas A. P. (1996) Cyclic GMP induces oscillatory calcium signals in rat hepatocytes. J. Biol. Chem. 271, 19,817–19,825.

    CAS  Google Scholar 

  91. Pozzan T., Rizzuto R., Volpe P., and Meldolesi J. (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol. Rev. 74, 595–635.

    PubMed  CAS  Google Scholar 

  92. Parys J. B., Sernett S. W., Delisle S., Synder P. M., Welsh M. J., and Campbell K. P. (1992) Isolation, characterization and location of the 1,4,5-trisphosphate receptor protein in Xenopus laevis oocytes. J. Biol. Chem. 267, 18,776–18,782.

    CAS  Google Scholar 

  93. Wang Y., Lin S. Z., Chiou A. L., Williams L. R., and Hoffer B. J. (1997) Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex. J. Neurosci. 17, 4341–4348

    PubMed  CAS  Google Scholar 

  94. Blatteis C. M. (1990) Neuromodulative actions of cytokines. Yale J. Biol. Med. 63, 133–146.

    PubMed  CAS  Google Scholar 

  95. Katsuki H., Nakai S., Hirai Y., Akaji K., Kiso Y., and Satoh M. (1990) Interleukin-1 beta inhibits long-term potentiation in the CA3 region of mouse hippocampal slices. Eur. J. Pharmacol. 18, 323–326.

    Google Scholar 

  96. Miller L. G., Galpern W. R., Dunlap K., Dinarello C. A., and Turner T. J. (1991) Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. Biol. Pharmacol. 39, 105–108.

    CAS  Google Scholar 

  97. Spranger M., Lindholm D., Bandtlow C., Heumann R., Ghahn H., Näher-Noè M., and Thoenen H. (1990) Regulation of nerve growth factor (NGF) synthesis in the rat central nervous system: comparison between the effects of interleukin-1 and various growth factors in astrocyte cultures and in vivo. Eur. J. Neurosci. 2, 69–76.

    PubMed  Google Scholar 

  98. Guilian D., Woodward J., Young D. G., Krebs J. F., Lachman L. B. (1988) Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J. Neurosci 8, 2485–2489.

    Google Scholar 

  99. Rothwell N. J. (1990) Mechanisms of the pyrogenic actions of cytokines. Eur. Cytokine Network 1, 211–213.

    CAS  Google Scholar 

  100. Plata-Salaman C. R., Oomura Y., and Kai Y. (1988) Tumor necrosis factor and interleukin-1 beta: suppression of food intake by direct action in the central nervous system. Brain Res. 448, 106–114.

    PubMed  CAS  Google Scholar 

  101. Okumura T., Uehara A., Okamura K., Takasugi Y., and Namiki M. (1990) Inhibition of gastric pepsin secretion by peripherally or centrally injected interleukin-1 in rats. Biochem. Biophys Res. Commun. 67, 956–961.

    Google Scholar 

  102. Sternberg E. M. (1989) Monokines, lymphokines, and the brain. In The Year in Immunology (Cruse J.M. and Lewis R.E., eds.), Kargel, Basel, pp. 205–217.

    Google Scholar 

  103. Cornell R. P. and Schwartz D. B. (1989) Central administration of interleukin 1 elicits hyperinsulinemia in rats. Am. J. Physiol. 256, R772-R777.

    PubMed  CAS  Google Scholar 

  104. Opp M., Obal F Jr., and Krueger J. M. (1989) Corticotropin-releasing factor attenuates interleukin 1-induced sleep and fever in rabbits. Am. J. Physiol. 257, R528-R535.

    PubMed  CAS  Google Scholar 

  105. Tazi A., Dantzer R., Crestani F., and Le Moal M. (1990) Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity. Neurosci. Res. Commun. 1, 159–165.

    Google Scholar 

  106. Relton J. K. and Rothwell N. J. (1992) Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal damage in the rat. Brain Res. Bull. 29, 243–246.

    PubMed  CAS  Google Scholar 

  107. Martin D., Chinookoswong N., and Miller G. (1995) The interleukin-1 receptor antagonis (rhII-1ra) protects against cerebral infarction in a rat model of hypoxia-ischaemia. Exp. Neurol. 130, 362–367.

    Google Scholar 

  108. Doble A. (1995) Excitatory amino acid receptors and neurodegeneration. Therapie 50, 319–337.

    PubMed  CAS  Google Scholar 

  109. Martin D. and Near S. L. (1995) Protective effect of the interleukin-1 receptor antagonist (IL-1ra) on experimental allergic encephalomyelitis in rats. J. Neuroimmunol. 61, 241–245.

    PubMed  CAS  Google Scholar 

  110. Griffin W., Stanley L. C., Ling C., White L., MacLeod V., Perrot L. J., et al. (1990) Brain Interleukin-1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl. Acad. Sci. USA 86, 7611–7615.

    Google Scholar 

  111. Sheng J. G., Ito K., Skinner R. D., Mark R. E., Rovnaghi C. R., Van Eldik L. J., and Griffin W. S. (1996) In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis. Neurobiol. Aging 7, 761–766.

    Google Scholar 

  112. Rothwell J. G., Luheshi G., and Toulmond S. (1966) Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology. Pharmacol. Therapeuti. 69, 85–95.

    Google Scholar 

  113. Rothwell N. J. (1991) Functions and mechanisms of interleukin-1 in the brain. Trends Pharmacol. Sci. 12, 430–435.

    PubMed  CAS  Google Scholar 

  114. Rothwell N. J. (1999) Annual Review prize lecture cytokines-killers in the brain? J. Physiol. 514, 3–17.

    PubMed  CAS  Google Scholar 

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Correspondence to Mitri Palmi.

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Palmi, M., Meini, A. Role of the nitric oxide/cyclic GMP/Ca2+ signaling pathway in the pyrogenic effect of interleukin-1β. Mol Neurobiol 25, 133–147 (2002). https://doi.org/10.1385/MN:25:2:133

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