Role of the inducible forms of cyclooxygenase and nitric oxide synthase in inflammatory pain

Ferreira, Sérgio Henrique; Cunha, Femardo Q.; Hyslop, Stephen

doi:10.1007/978-3-0348-8747-2_7

Cited by 2 publications

(2 citation statements)

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“…Finally, the fact that neither biliverdine nor free iron has any thermoregulatory role in the CNS of rats leads to the rationale that CO is likely to be the HO product with a pyretic action. Because the majority of CO actions have been shown to be mediated by activation of sGC, we tested the effect of the sGC inhibitor ODQ (11,27) on the rise in T c evoked by heme overload. Intracerebroventricular administration of ODQ only led to a slight increase in T c (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Protocol 5: determination of the effect of the sGC inhibitor ODQ on the intracerebroventricular heme-induced rise in T c . After T ci was measured rats were injected intracerebroventricularly with ODQ (1 g in 4 l), a sGC inhibitor (11,27) or its vehicle (4 l of 1% DMSO in saline). The dose of ODQ was chosen on the basis of previous studies (11,15,46) and because when preliminary doses were tested the dose of 1 g intracerebroventricularly produced the most consistent and repeatable results.…”

Section: Experimental Protocolsmentioning

confidence: 99%

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Carbon monoxide is the heme oxygenase product with a pyretic action: evidence for a cGMP signaling pathway

Steiner

Branco

2001

American Journal of Physiology-Regulatory, Integrative and Comp

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We have recently reported that the central heme oxygenase (HO) pathway has an important role in the genesis of lipopolysaccharide fever. However, the HO product involved, i.e., biliverdine, free iron, or carbon monoxide (CO), has not yet been identified with certainty. Therefore, in the present study, we tested the thermoregulatory effects of all HO products. Body core temperature (T(c)) and gross activity of awake, freely moving rats was measured by biotelemetry. Intracerebroventricular administration of heme-lysinate (152 nmol), which induces the HO pathway, evoked a marked increase in T(c), a response that was attenuated by intracerebroventricular pretreatment with the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (200 nmol), indicating that an HO product has a pyretic action in the central nervous system (CNS) of rats. Besides, heme-lysinate also increased gross activity, but no correlation was found between this effect and the increase in T(c). Moreover, intracerebroventricular biliverdine or iron salts at 152 nmol, a dose at which heme-lysinate was effective in increasing T(c), produced no change in T(c). Accordingly, intracerebroventricular treatment with the iron chelator deferoxamine elicited no change in basal T(c) and did not affect heme-induced pyresis. However, heme-induced pyresis was completely prevented by the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one. Because biliverdine and iron had no thermoregulatory effects and CO produces most of its actions via sGC, these data strongly imply that CO is the only HO product with a pyretic action in the CNS.

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Section: Discussionmentioning

confidence: 99%