RGD Reference Report - Endothelin-1 as a central mediator of LPS-induced fever in rats. - Rat Genome Database

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Endothelin-1 as a central mediator of LPS-induced fever in rats.

Authors: Fabricio, AS  Rae, GA  D'Orleans-Juste, P  Souza, GE 
Citation: Fabricio AS, etal., Brain Res. 2005 Dec 20;1066(1-2):92-100.
RGD ID: 4144129
Pubmed: PMID:16360659   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2005.10.037   (Journal Full-text)

Fever induced by E. coli lipopolysaccharide (LPS) in rats is substantially reduced by blockade of central endothelin ET(B) receptors. This study explores the role of endothelin-1 as a central mediator of fever in rats, by investigating the effect of a pyrogenic dose of LPS on the levels of big endothelin-1 and endothelin-1 in the cerebrospinal fluid (CSF) and endothelin-1 in the plasma. We further assessed whether the increase in body temperature caused by central injection of endothelin-1 constitutes solely a hyperthermia or a true integrated febrile response. LPS (5 mug kg(-1), i.v.) induced fever which peaked at 1.16 +/- 0.24 degrees C within 2 h and remained stable up to 5 h. CSF levels of immunoreactive (ir) big endothelin-1 decreased to undetectable levels at 3 h after LPS, returning only partially at 5 h post-injection. CSF ir-endothelin-1 levels were undetectable in saline-treated animals, but reached 21.9 +/- 5.2 fmol ml(-1) at 3 h after LPS treatment. Plasma ir-endothelin-1 levels were unchanged after saline or LPS. Central injection of endothelin-1 (1 pmol, i.c.v.) caused long-lasting increases in body temperature (0.81 +/- 0.17 degrees C, 3 h), but simultaneously decreased tail skin temperature (-1.10 +/- 0.26 degrees C), indicating cutaneous vasoconstriction. Moreover, endothelin-1 induced fever (1.0 +/- 0.3 degrees C, 3 h) when injected into the preoptic area of the anterior hypothalamus (100 fmol), but not i.v. (1 or 10 pmol). These data suggest that endothelin-1 is produced in the brain and acts centrally as a mediator of LPS-induced fever.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Edn1Ratresponse to lipopolysaccharide  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Edn1  (endothelin 1)


Additional Information