The relevance of kalikrein-kinin system via activation of B-2 receptor in LPS-induced fever in rats

Autor(es)

Soares, Denis de Melo ^[1] ; Santos, Danielle R. ^[2] ; Rummel, Christoph ^[3] ; Ott, Daniela ^[3] ; Melo, Miriam C. C. ^[2] ; Roth, Joachim ^[3] ; Calixto, Joao B. ^[4] ; Souza, Gloria E. P. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Bahia, Fac Pharm, Dept Medicament, Lab Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Phys & Chem, Fac Pharmaceut Sci, Pharmacol, Ribeirao Preto, SP - Brazil

^[3] Justus Liebig Univ Giessen, Vet Physiol, Fac Vet Med, Giessen - Germany

^[4] Ctr Innovat & Preclin Res, Florianopolis, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuropharmacology; v. 126, p. 84-96, NOV 2017.
• Citações Web of Science: 5

Resumo

Purpose: This study evaluated the involvement of endogenous kallikrein-kinin system and the bradykinin (BK) B-1 and B-2 receptors on LPS-induced fever and the POA cells involved in this response. Material and methods: Male Wistar rats received either i.v. (1 mg/kg), i.c.v. (20 nmol) or i.h. (2 nmol) injections of icatibant (B-2 receptor antagonist) 30 or 60 min, respectively, before the stimuli. DALBK (B-1 receptor antagonist) was given either 15min before BK (i.c.v.) or 30 min before LPS (i.v.). Captopril (5 mg/kg, sc.,) was given 1 h prior LPS or BK. Concentrations of BK and total kininogenon CSF, plasma and tissue kallikrein were evaluated. Rectal temperatures (rT) were assessed by telethermometry. Ca++ signaling in POA cells was performed in rat pup brain tissue microcultures. Results: Icatibant reduced LPS fever while, captopril exacerbated that response, an effect abolished by icatibant. Icatibant (i.h.) reduced fever to BK (i.h.) but not that induced by LPS (i.v.). BK increased intracellular calcium concentration in neurons and astrocytes. LPS increased levels of bradykinin, tissue kallikrein and total kininogen. BK (i.c.v.) increased rT and decreased tail skin temperature. Captopril potentiated BK-induced fever an effect abolished by icatibant. DALBK reduced the fever induced by BK. BK (i.c.v.) increased the CSF PGE(2)concentration. Effect abolished by indomethacin (i.p.). Conclusions: LPS activates endogenous kalikrein-kinin system leading to production of BK, which by acting on B-2-receptors of POA cells causes prostaglandin synthesis that in turn produces fever. Thus, a kinin B-2-receptor antagonist that enters into the brain could constitute a new and interesting strategy to treat fever. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 08/10323-3 - Investigação dos mecanismos celulares e moleculares centrais envolvidos na febre induzida pela CCL3/MIP-1alpha
• Beneficiário: Denis de Melo Soares
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 97/09837-6 - Mecanismos e mediadores envolvidos na integração das respostas inflamatória e febril
• Beneficiário: Glória Emília Petto de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Temático