Archives of Pharmacal Research

  • 제24권6호
  • /
  • Pages.607-612
  • /
  • 2001
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Effects of Heme Oxygenase System on the Cyclooxygenase in the Primary Cultured Hypothalamic Cells

  • Lee, Hae-Uk (Lab of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Lee, Hee-Jee (Lab of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Park, Ha-Young (Lab of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Lee, Sang-Ho (Lab of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Jang, Choon-Gon (Lab of Pharmacology, College of Pharmacy, Sungkyunkwan University) ;
  • Lee, Seok-Yong (Lab of Pharmacology, College of Pharmacy, Sungkyunkwan University)
  • 발행 : 2001.12.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Endogenous carbon monoxide (CO) shares with nitric oxide (NO) a role as a putative neural messenger in the brain. Both gases are believed to modulate CNS function via an increase in cytoplasmic cGMP concentrations secondary to the activation of soluble guanylate cyclase (sGC). Recently CO and NO were proposed as a possible mediator of febrile response in hypothalamus. NO has been reported to activate both the constitutive and inducible isoform of the cyclooxygenase (COX). Thus, we investigated whether CO arising from heme catabolism by heme oxygenate (HO) is involved in the febrile response via the activation of COX in the hypothalamus. $PGE_2$ which is a final mediator of febrile response released from primary cultured hypothalamic cells was taken as a marker of COX activity. $PGE_2$ concentration was measured with EIA kits. Exogenous CO (CO-saturated medium) and hemin (a substrate and potent inducer of HO) evoked an increase in $PGE_2$ release from hypothalamic cells, and these effects were blocked by methylene blue (an inhibitor of sGC). And membrane permeable cGMP analogue, dibutyryl-cGMP elicited significant increases in $PGE_2$release. These results suggest that there may be a functional link between HO and COX enzymatic activities. The gaseous product of hemin through the HO pathway, CO, might play a role through the modulation of the COX activity in the hypothalamus.

키워드

참고문헌

  1. Can. J. Physiol. Pharmacol. v.65 Prostaglandin formation in feline cerebral microvessels: effect of endotoxin and interleukin-1 Bishai,I;Dinarello,C.A.;Coceani,F.
  2. J. Comp. Neurol. v.355 Characterization of inducible cyclooxygenase in the rat brain Breder,C.D.;Dewitt,D.L.;Kraig,R.P.
  3. Brain Res. v.733 Endothelial cells of the brain vasculature express cyclooxygenase-2 mRNA in response to systemic interleukin-1: a possible site of prostaglandin synthesis responsible for fever Cao,C.;Mastsumura,K.;Yamagata,K.;Watanabe,Y.
  4. Brain Res. v.697 Induction by lipopolysaccharide of cyclooxygenase-2mRNA in rat brain; its possible role in the febrile response Cao,C.;Mastsumura,K.;Yamagata,K.Watanabe,Y.
  5. J. Endocrinol. v.116 Comparison of peptide release from fetal rat hypothalamic neurones culture in defined media and serum-containing media Clarke,M.J.;Gillies,G.E.
  6. Fever: basic mechanisms and management Prostaglandins and fever: facts and controversies Coceani,F.;Mackowiak,P.(Ed.)
  7. J. Infect. Dis. v.179 no.SUP.2 Cytokines as endogenous pyrogens Dinarello,C.A.
  8. Br. J. Pharmacol. v.125 Essential role for endothelin ETB receptors in fever induced by LPS(E.coli) in rats Fabricio,A.S.C.;Silva,C.A.A.;Rae,G.A.;D'Orleans-Juste,P.;Souza,G.E.P.
  9. J. Endocrinol. v.149 Gaseous transmitters as new agents in neuroendocrine regulation Gosta,A.;Poma,A.;Navarra,P.;Forsling,M.L.;Grossman,A.
  10. Neuroendocrinology v.62 Production of systemic and hypothalamic cytokines during the early phases of the endotoxin fever Jansky,L.;Vybiral,S.;Pospisilowa,D.;Roth,J.;Dornand,J.;Zeisberger,E.;Kaminkowa,J.
  11. Kor. J. Physiol. Pharmacol. v.5 The hyterthermic effect of nitric oxide in central nervous system Jung,J.K.;Sohn,U.D.;Lee,S.Y.
  12. Endocrinology v.124 Interleukin-1 increase prostaglandin E₂in rat astrocyte cultures: modulatory effect of neuropeptides Katsuura,G.;Gottschall,P.E.;Dahl,R.R.;Arimura,A.
  13. Proc. Natl. Acad.Sci. U.S.A. v.92 Basis of guanylate cyclase activation by carbon monoxide Kharitonov,V.G.;Sharma,V.S.;Pilz,R.B.;Magde,D.;Koesling,D.
  14. Am. J. Physiol. v.266 Interleukin-1 beta causes the increase in anterior hypothalamic interleukin-6 during LPS-induced fever in rats Klir,J.J.;McClellan,J.L.;Kluger,M.J.
  15. Physiol. Rev. v.71 Fever: role of pyrogens and cryogens Kluger,M.J.
  16. Am. J. Physiol. v.258 Role of interleukin-6 in fever in the rat LeMay,L.G.;Vander,A.J.;Kluger,M.J.
  17. Br. J. Pharmacol. v.118 Nitric oxide synthase-cyclo-oxy-genase pathways in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits Lin,J.H.;Lin,M.T.
  18. Annu. Rev. Pharmacol. Toxicol. v.37 The heme oxygenase system: A regulator of second messenger gases Maines,M.D.
  19. J. Physiol. v.454 Thermal and PGE₂sensitivity of the organum vasculosum laminae terminalis region and preoptic area in rat brain slices Matsuda,T.;Hori,T.;Nakashima,T.
  20. Brain Res. v.533 High density of prostaglandin E₂binding sites in the anterior wall of the 3rd ventricle - a possible site of its hyperthermic action Matsumura,K.;Watanabe,Y.;Onoe,H.;Hayaishi,O.
  21. Eur. J. Biochem. v.247 Isolation and characterization of a cDNA from the rat brain that encodes heme protein heme oxygenase-3 McCoubrey,W.M.;Huang,T.J.;Maines,M.D.
  22. J. Neurochem. v.66 Interferon-and nitric oxide down-regulate lipopolysaccharide-induced prostanoid production in cultured rat microglial cells by inhibiting cyclooxygenase-2 expression Minghetti,L.;Polazzi,E.;Nicolini,A.;Creminon,C.;Levi,G.
  23. Glia v.15 Evidence for cyclooxygenase activation by nitric oxide in astrocytes Molina-Holgado,F.;Loedo,A.;Guaza,C.
  24. J. Physiol. v.397 Multiple control of fever production in the central nervous system of rabbits Morimoto,A.;Murakami,N.;Nakamori,T.;Watanabe,T.
  25. The Rat Brain in Stereotaxic Coordinates(3rd ed.) Paxinos,G.;Watson,C.
  26. Brain Res. v.802 Cyclooxygenase 2 mRNA expression in rat brain after peripheral injection of lipopolysaccharide Quan,N.;Whiteside,M.;Herkenham,M.
  27. Am. J. Physiol. v.265 Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in the guinea pig Roth,J.;Conn,C.A.;Kluger,M.J.;Zeisberger,E.
  28. Life Sci. v.62 Inhibition of nitric oxide synthase results in a suppression of interleukin-1-induced fever in rats Roth,J.;Storr,B.;Voigt,K.Zeisberger,E.
  29. Proc. Natl. Acad. Sci. U.S.A. v.90 Nitric oxide activates cyclooxygenase enzymes Salvemini,D.;Misko,T.P.;Masferrer,J.L.;Seibert,K.;Currie,M.G.;Needleman,P.
  30. J. Clin. Invest. v.93 Endogenous nitric oxide enhances prostagladin production in a model of renal inflammation Salvemini,D.;Seibert,K.;Masferrer,J.L.;Misko,T.P.;Currie,M.G.;Needleman,P.
  31. Am. J. Physiol. v.271 Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysacchaide fever Scammell,T.E.;Elmquist,J.K.;Saper,C.B.
  32. Biochem. Biophys. Acta. v.1083 Prostaglandin endoperoxide synthase: structure and catalysis Smith,W.L.;Marnett,L.J.
  33. Am. J. Physiol. Regul. Integr. Comp. Physiol. v.280 Carbon monoxide is the heme oxygenase product with a pyretic action: evidence for a cGMP signaling pathway Steiner,A.A.;Branco,L.G.
  34. J. Appl. Physol. v.88 Central CO-heme oxygenase pathway raises body temperature by a prostaglandin-independent way Steiner,A.A.;Branco,L.G.
  35. Am. J. Physol. v.277 Carbon monoxide as a novel mediator of the febrile response in the central nervous system Steiner,A.A.;Colombari,E.;Branco,L.G.
  36. J. Physiol. v.432 Differential sensitivity in the sites of fever production by prostaglandin-E₁within the hypothalamus of the rat Stitt,J.T.
  37. J. Biol. Chem. v.265 Developmental expression of heme oxygenase isozymes in rat brain. Two HO-2 mRNAs are detected Sun,Y.;Rotenberg,M.O.;Maines,M.D.
  38. Ann. N.Y. Acad. Sci. v.813 Role of substance P(SP) in the mediation of endotoxin(LPS) fever in rats Szelenyi,Z.;Sezekely,M.;Blalsko,M.
  39. Free Radic. Biol. Med. v.26 Superoxide generation from constitutive nitric oxide synthase in astrocytes in vitro regulates extracellular nitric oxide availability Tolias,C.M.;McNeil,C.J.Jurate,K.;Hillhouse,E.W.
  40. Brain Res v.543 Localization of prostaglandin endoperoxide synthase in neurons and glia in monkey brain Tsubokura,S.;Watanabe,Y.;Ehara,H.;Imamura,K.;Sugimoto,O.;Kagamiyama,H.;Yamanoto,S.;Hayaishi,O.
  41. J. Immunol. v.146 IL-8 in septic shock, endotoxemia, and after IL-1 administration Van Zee,K.J.;DeForge,L.E.;Fischer,E.;Marano,M.A.;Kenney,J.S.;Remick,D.G.;Lowry,S.F.;Moldawer,L.L.
  42. Biochem. Biophys. Acta v.572 On the hemoprotein character of prostaglandin endoperoxide synthetase Vander Ouderaa,F.J.;Buytenhek,M;Slikkerveer,F.J.;VanDorp,D.A.
  43. Science v.259 Carbon monoxide: a putative neural messenger Verma.A.;Hirsh,D.J.;Glatt,C.E.;Ronnett,G.V.;Snyder,S.H.
  44. Curr. Pharm. Des. v.6 Cyclooxygenases in the central nervous system: Implications for treatment of neurological disorders Yermakova,A.;O'Banion,M.K.
  45. Mediatiors Inflamm. v.3 A pre-formed pyrogenic factor released by lipopolysaccharide stimulated macrophages Zampronio,A.R.;Melo,M.C.C.;Silva,C.A.A.;Pela,I.R.;Hopkins,S.J.;Souza,G.E.P.
  46. Am. J. Physiol. v.266 Interleukin-8 induces fever by a prostaglandin-independent mechanism Zampronio,A.R.;Souza,G.E.P.;Silva,C.A.A.;Cunha,F.Q.;Ferreira,S.H.
  47. J. Thermal. Biol. v.24 From humoral fever to neuroimmunollogical control of fever Zeisberger,E.