5-Iodoresiniferatoxin evokes hypothermia in mice and is a partial transient receptor potential vanilloid 1 agonist in vitro

Isao Shimizu, Tohko Iida, Nobuhiko Horiuchi, Michael J. Caterina

Research output: Contribution to journalArticlepeer-review

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated ion channel required for normal in vivo responses to these painful stimuli. However, growing evidence suggests that TRPV1 also participates in thermoregulation. Therefore, we examined the effects of a selective TRPV1 antagonist, 5-iodoresiniferatoxin (I-RTX), on mouse body temperature. Surprisingly, s.c. administration of I-RTX (0.1-1 μmol/kg) evoked a hypothermic response similar to that evoked by capsaicin (9.8 μmol/kg) in naive wild-type mice, but not in mice pretreated with resiniferatoxin, a potent TRPV1 agonist, or in naive TRPV1-null mice. In response to I-RTX in vitro, HEK293 cells expressing rat TRPV1 exhibited increases in intracellular Ca 2+ (biphasic, EC50 = 56.7 nM and 9.9 μM) that depended on Ca2+ influx and outwardly rectifying, capsazepine-sensitive currents that were smaller than those evoked by 1 μM capsaicin. Thus, I-RTX induces TRPV1-dependent hypothermia in vivo and is a partial TRPV1 agonist in vitro.

Original languageEnglish (US)
Pages (from-to)1378-1385
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume314
Issue number3
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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