[show abstract]
[hide abstract]
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 oxygenase (HO) is involved in the febrile 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 EIA kits. Exogenous CO (CO-saturated medium) and hemin (a substrate and potent inducer of
HO) evoked an increase in PGE2 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 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.
Archives of Pharmacal Research 04/2012; 24(6):607-612. · 1.59 Impact Factor
