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Central substance P NK(1) receptors are involved in fever induced by LPS but not by IL-1β and CCL3/MIP-1α in rats.
MedLine Citation:
PMID:  21303668     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Substance P (SP) is a neuropeptide that can modulate inflammatory mediator release through activation of NK(1) receptors (NK(1)R). Some studies have also suggested the involvement of SP in lipopolysaccharide (LPS)-induced fever. However, the precise contribution of this neuropeptide to the pathways activated during fever is unknown. In this study we investigated the effect of a selective NK(1)R antagonist, SR140333B, on the febrile response induced by LPS and cytokines. Our results show that the systemic injection of SR140333B did not modify the fever induced by LPS at a dose that is able to reduce protein extravasation induced by SP in the skin. On the other hand, intracerebroventricular administration of SR140333B significantly reduced the fever induced by peripheral injection of LPS. These data emphasize an important role for SP in the central nervous system during the febrile response to LPS, and are reinforced by the fact that intracerebroventricular injection of SP also induced fever in a dose-dependent manner in captopril-treated rats. Considering that the febrile response can result from the generation of several endogenous pyrogens, among them interleukin (IL)-1β and macrophage inflammatory protein-1α (CCL3/MIP-1α), we also examined the effect of SR140333B on the fever induced by these cytokines which act through prostaglandin-dependent and independent mechanisms, respectively. Surprisingly, SR140333B did not modify the febrile response to IL-1β or CCL3/MIP-1α. Altogether these data suggest that the central action of SP is essential for LPS, but not for IL-1β or CCL3/MIP-1α-induced fever.
Authors:
Renata Cristiane Dos Reis; Haissa de Oliveira Brito; Daniel Fraga; Daniela de Almeida Cabrini; Aleksander Roberto Zampronio
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-5
Journal Detail:
Title:  Brain research     Volume:  -     ISSN:  1872-6240     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier B.V.
Affiliation:
Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil.
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