Role of the locus coeruleus carbon monoxide pathway in endotoxin fever in rats.
Carbon monoxide (CO) has been identified as a diffusible signaling messenger in the brain, capable of altering body temperature by stimulating soluble guanylate cyclase (sGC). However, its site of action remains unclear. Locus coeruleus (LC) is rich not only in sGC but also in heme oxygenase (HO; the enzyme that catalyses the metabolism of heme to CO, along with biliverdin and free iron). Therefore, the possible role of the HO-CO-cGMP pathway in the lipopolysaccharide (LPS)-induced fever regulation by LC neurones was investigated. Induction of the HO pathway using heme-lysinate (7.6 nmol, intra-LC) attenuated the febrile response, and this effect could be prevented by pretreatment with ODQ (an sGC inhibitor; given intracerebroventricularly, 1.3 nmol). Moreover, ZnDPBG (an HO inhibitor; 5 nmol, intra-LC) augmented the febrile response. Taken together, these data suggest that CO in the LC produced by the HO pathway and acting via cGMP plays an antipyretic role during LPS-fever in rats.
Ravanelli
Maria Ida Bonini
MI
Department of Physiology, Medical School of Ribeirão Preto, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
Almeida
Maria C
MC
Branco
Luiz G S
LG
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism / Q000502:physiology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C106087:heme lysinate; D006418:Heme; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008239:Lysine