α2-, α2A-, α2B/2C-Adrenoceptor subtype antagonists prevent lipopolysaccharide-induced fever response in rabbits

Agnes Bencsics, Ilia J. Elenkov, E. Sylvester Vizi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Exogenous pyrogens, e.g., bacterial lipopolysaccharides (LPS), are thought to stimulate macrophages to release endogenous pyrogens, e.g., TNFα, IL-1 β, and IL-6, which act in the hypothalamus to produce fever. We studied the effect of different α1- and α2-adrenoceptor subtype antagonists, applied intraperitoneally, on the febrile response induced by LPS in rabbits. Evidence was obtained that prazosin, an α1- and α2B/2C-adrenoceptor antagonist; WB-4101, an α1- and α2A-adrenoceptor antagonist; CH-38083, a highly selective α2-adrenoceptor antagonist (α2: α1 > 2000); BRL-44408, an α2A-adrenoceptor antagonist; and ARC-239, an α2B/2C- and also α1-adrenoceptor antagonist, blocked the increase of colonic temperature of the rabbit produced by 2 μg/kg LPS administered intravenously without being able in themselves to affect colonic temperature. In addition, prazosin, WB-4101 and CH-38083 antagonized the fall in skin temperature that occurred at the time when the colonic temperature was rising in control animals injected with LPS. All these results suggest that norepinephrine, through stimulation of both α1-andα2-2A-andα2B/2C-) adrenoceptor subtypes, is involved in producing fever in response to bacterial LPS.

Original languageEnglish
Pages (from-to)302-306
Number of pages5
JournalBrain research
Volume705
Issue number1-2
DOIs
Publication statusPublished - Dec 24 1995

Keywords

  • Fever
  • Lipopolysaccharide
  • Norepinephrine
  • Rabbit
  • Sympathetic nervous system
  • α-Adrenoceptor
  • α-Adrenoceptor subtype

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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