Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism independent of the subtype-1 vanilloid receptor

M. Devrim Dogan, Shreya Patel, Alla Y. Rudaya, Alexandre A. Steiner, Miklós Székely, Andrej A. Romanovsky

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Abstract

As pretreatment with intraperitoneal capsaicin (8-methyl-N-vanillyl-6- nonenamide, CAP), an agonist of the vanilloid receptor known as VR1 or transient receptor potential channel-vanilloid receptor subtype 1 (TRPV-1), has been shown to block the first phase of lipopolysaccharide (LPS) fever in rats, this phase is thought to depend on the TRPV-1-bearing sensory nerve fibers originating in the abdominal cavity. However, our recent studies suggest that CAP blocks the first phase via a non-neural mechanism. In the present work, we studied whether this mechanism involves the TRPV-1. Adult Long-Evans rats implanted with chronic jugular catheters were used. Pretreatment with CAP (5 mgk g -1, i.p.) 10 days before administration of LPS (10 μg kg -1, i.v.) resulted in the loss of the entire first phase and a part of the second phase of LPS fever. Pretreatment with the ultrapotent TRPV-1 agonist resiniferatoxin (RTX; 2, 20, or 200 μg kg -1, i.p.) 10 days before administration of LPS had no effect on the first and second phases of LPS fever, but it exaggerated the third phase at the highest dose. The latter effect was presumably due to the known ability of high doses of TRPV-1 agonists to cause a loss of warm sensitivity, thus leading to uncontrolled, hyperpyretic responses. Pretreatment with the selective competitive TRPV-1 antagonist capsazepine (N-[2-(4-chlorophenyl) ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2- benzazepine-2-carbothioamidem, CPZ; 40 mg kg -1, i.p.) 90 min before administration of LPS (10 μg kg -1, i.v.) or CAP (1 mg kg -1, i.p.) did not affect LPS fever, but blocked the immediate hypothermic response to acute administration of CAP. It is concluded that LPS fever is initiated via a non-neural mechanism, which is CAP-sensitive but RTX- and CPZ-insensitive. The action of CAP on this mechanism is likely TRPV-1-independent. It is speculated that this mechanism may be the production of prostaglandin E 2 by macrophages in LPS-processing organs.

Original languageEnglish
Pages (from-to)1023-1032
Number of pages10
JournalBritish journal of pharmacology
Volume143
Issue number8
DOIs
Publication statusPublished - Dec 1 2004

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Keywords

  • Body temperature
  • Capsazepine
  • Cholecystokinin
  • Endotoxin
  • Eye-wiping response
  • Iodo-resiniferatoxin
  • Satiety
  • TRPV-1
  • Thermoregulation
  • VR1

ASJC Scopus subject areas

  • Pharmacology

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