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The Pharmaceutical Society of Korea (대한약학회)
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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)
  • Published : 2001.12.01
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Abstract

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.

Keywords

References

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