Document Detail

Propyretic role of the locus coeruleus nitric oxide pathway.
MedLine Citation:
PMID:  20176679     Owner:  NLM     Status:  MEDLINE    
Nitric oxide has been reported to modulate fever in the brain. However, the sites where NO exerts this modulation remain somewhat unclear. Locus coeruleus (LC) neurons express not only nitric oxide synthase (NOS) but also soluble guanylyl cyclase (sGC). In the present study, we evaluated in vivo and ex vivo the putative role of the LC NO-cGMP pathway in fever. To this end, deep body temperature was measured before and after pharmacological modulations of the pathway. Moreover, nitrite/nitrate (NOx) and cGMP levels in the LC were assessed. Conscious rats were microinjected within the LC with a non-selective NOS inhibitor (N(G)-monomethyl-l-arginine acetate), a NO donor (NOC12), a sGC inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) or a cGMP analogue (8-bromo-cGMP) and injected intraperitoneally with endotoxin. Inhibition of NOS or sGC before endotoxin injection significantly increased the latency to the onset of fever. During the course of fever, inhibition of NOS or sGC attenuated the febrile response, whereas microinjection of NOC12 or 8-bromo-cGMP increased the response. These findings indicate that the LC NO-cGMP pathway plays a propyretic role. Furthermore, we observed a significant increase in NOx and cGMP levels, indicating that the febrile response to endotoxin is accompanied by stimulation of the NO-cGMP pathway in the LC.
Renato N Soriano; Maria I Ravanelli; Marcelo E Batalhao; Evelin C Carnio; Luiz G S Branco
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-22
Journal Detail:
Title:  Experimental physiology     Volume:  95     ISSN:  1469-445X     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  669-77     Citation Subset:  IM    
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 - Ribeirão Preto, SP, Brazil.
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MeSH Terms
Cyclic GMP / analogs & derivatives,  pharmacology
Endotoxins / pharmacology
Fever / chemically induced*,  metabolism,  physiopathology*
Guanylate Cyclase / antagonists & inhibitors
Locus Coeruleus / drug effects,  metabolism*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / physiology
Nitroso Compounds / pharmacology
Oxadiazoles / pharmacology
Quinoxalines / pharmacology
Rats, Wistar
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
Reg. No./Substance:
0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Endotoxins; 0/NOC 12; 0/Nitroso Compounds; 0/Oxadiazoles; 0/Quinoxalines; 0/Receptors, Cytoplasmic and Nuclear; 10102-43-9/Nitric Oxide; 31356-94-2/8-bromocyclic GMP; 50903-99-6/NG-Nitroarginine Methyl Ester; 7665-99-8/Cyclic GMP; EC Cyclase; EC guanylyl cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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