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KMID : 0043320010240060607
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Archives of Pharmacal Research
2001 Volume.24 No. 6 p.607 ~ p.612
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Effects of Heme Oxygenase System on the Cyclooxygenase in the Primary Cultured Hypothalamic Cells
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Lee HU
Lee HJ/Park HY/Lee SH/Jang CG/Lee SY
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Abstract
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Endogenous carbon monoxide (CO) shares with nitric oxide (N0) 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 isofrom of the cyclooxygenase(COX). Thus, we investiagted whether CO arising form heme catabolism by heme oxygenase(HO) is involved in the febrille response via the activation of COX in the hypothalamus. PGE2 which is a final mediator of febrile response released from primary cultured hypothalamic cells was taken as a marker of COX activity. PGE2 concentration was measured with ELA kits. Exogenous CO (CO-saturated medium) and hemin (a substrate and potent Inducer of HO) evoked an increase in PCIB release from hypothalamic cells, and these effects were blocked by methylene blue (an inhibitor of Sgc). And membrane permeable CCMP analogue, dibutyry1-Ccmp elicited significant increases in PGE2 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.
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