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The relevance of kalikrein-kinin system via activation of B2 receptor in LPS-induced fever in rats.
Neuropharmacology. 2017 Nov; 126:84-96.N

Abstract

PURPOSE

This study evaluated the involvement of endogenous kallikrein-kinin system and the bradykinin (BK) B1 and B2 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 (B2 receptor antagonist) 30 or 60 min, respectively, before the stimuli. DALBK (B1 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 PGE2concentration. Effect abolished by indomethacin (i.p.).

CONCLUSIONS

LPS activates endogenous kalikrein-kinin system leading to production of BK, which by acting on B2-receptors of POA cells causes prostaglandin synthesis that in turn produces fever. Thus, a kinin B2-receptor antagonist that enters into the brain could constitute a new and interesting strategy to treat fever.

Authors+Show Affiliations

Department of Medicament, Faculty of Pharmacy of Federal University of Bahia, Laboratory of Pharmacology, Ribeirão Preto, SP, Brazil. Electronic address: denisms@ufba.br.Pharmacology, Department of Physic and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil.Veterinary Physiology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Germany.Veterinary Physiology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Germany.Pharmacology, Department of Physic and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil.Veterinary Physiology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Germany.Center of Innovation and Preclinical Research, Florianópolis, SC, Brazil.Pharmacology, Department of Physic and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: gepsouza@fcfrp.usp.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28826826

Citation

Soares, Denis de Melo, et al. "The Relevance of Kalikrein-kinin System Via Activation of B2 Receptor in LPS-induced Fever in Rats." Neuropharmacology, vol. 126, 2017, pp. 84-96.
Soares DM, Santos DR, Rummel C, et al. The relevance of kalikrein-kinin system via activation of B2 receptor in LPS-induced fever in rats. Neuropharmacology. 2017;126:84-96.
Soares, D. M., Santos, D. R., Rummel, C., Ott, D., Melo, M. C. C., Roth, J., Calixto, J. B., & Souza, G. E. P. (2017). The relevance of kalikrein-kinin system via activation of B2 receptor in LPS-induced fever in rats. Neuropharmacology, 126, 84-96. https://doi.org/10.1016/j.neuropharm.2017.08.019
Soares DM, et al. The Relevance of Kalikrein-kinin System Via Activation of B2 Receptor in LPS-induced Fever in Rats. Neuropharmacology. 2017;126:84-96. PubMed PMID: 28826826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The relevance of kalikrein-kinin system via activation of B2 receptor in LPS-induced fever in rats. AU - Soares,Denis de Melo, AU - Santos,Danielle R, AU - Rummel,Christoph, AU - Ott,Daniela, AU - Melo,Míriam C C, AU - Roth,Joachim, AU - Calixto,João B, AU - Souza,Glória E P, Y1 - 2017/08/19/ PY - 2016/10/12/received PY - 2017/08/05/revised PY - 2017/08/11/accepted PY - 2017/8/23/pubmed PY - 2018/6/13/medline PY - 2017/8/23/entrez KW - B(1) and B(2) kinin receptors KW - Central mediation of fever KW - Hypothalamic pre-optic area KW - LPS KW - PGE(2) KW - Rats SP - 84 EP - 96 JF - Neuropharmacology JO - Neuropharmacology VL - 126 N2 - PURPOSE: This study evaluated the involvement of endogenous kallikrein-kinin system and the bradykinin (BK) B1 and B2 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 (B2 receptor antagonist) 30 or 60 min, respectively, before the stimuli. DALBK (B1 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 PGE2concentration. Effect abolished by indomethacin (i.p.). CONCLUSIONS: LPS activates endogenous kalikrein-kinin system leading to production of BK, which by acting on B2-receptors of POA cells causes prostaglandin synthesis that in turn produces fever. Thus, a kinin B2-receptor antagonist that enters into the brain could constitute a new and interesting strategy to treat fever. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/28826826/The_relevance_of_kalikrein_kinin_system_via_activation_of_B2_receptor_in_LPS_induced_fever_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(17)30386-6 DB - PRIME DP - Unbound Medicine ER -