title: Fever induced by platelet-derived growth factor, in contrast to fever induced by lipopolysaccharide, depends only on nitric oxide, but not on carbon monoxide pathway.
abstract: Platelet-derived growth factor (PDGF) is a multifunctional protein which is known to induce a febrile response when injected intracerebroventricularly. The gaseous neurotransmitters, nitric oxide (NO) and carbon monoxide (CO), are both known to exert thermoregulatory effects and to participate in lipopolysaccharide-induced fever. In this study, we investigated the role of NO and CO in the febrile response to PDGF-BB in rats. Intracerebroventricular (i.c.v.) injection of PDGF-BB produced a dose-dependent increase in body temperature. This increase in body temperature induced by PDGF-BB was exacerbated by N(G)-nitro-L-arginine methyl ester (L-NAME-a nonselective NO synthase inhibitor) and S-methyl-L-thiocitrulline treatment [SMTC-a neuronal NOS (nNOS) selective inhibitor], but not by aminoguanidine treatment [an inducible NOS (iNOS) selective inhibitor]. Zinc deuteroporphyrin 2,4-bis glycol treatment (ZnDPBG-a nonselective heme oxygenase (HO) blocker) did not affect PDGF-BB fever. Our data indicate that the NO but not the CO pathway participates in PDGF-BB fever. Furthermore, our data show that nNOS is the NOS isoform responsible for NO synthesis in this response.
authors.affiliation: Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Maria Camila
authors.initials: MC
authors.lastname: Almeida
authors.forename: Irene Rosemir
authors.initials: IR
authors.lastname: Pelá
authors.forename: Luiz Guilherme S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology*; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003905:Deuteroporphyrins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000502:physiology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D003905:Deuteroporphyrins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D000077214:Becaplermin; D002956:Citrulline; D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D013890:Thiourea; C086717:S-methylthiocitrulline; D019331:NG-Nitroarginine Methyl Ester