RT Journal Article SR Electronic T1 5-Iodoresiniferatoxin Evokes Hypothermia in Mice and Is a Partial Transient Receptor Potential Vanilloid 1 Agonist in Vitro JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1378 OP 1385 DO 10.1124/jpet.105.084277 VO 314 IS 3 A1 Isao Shimizu A1 Tohko Iida A1 Nobuhiko Horiuchi A1 Michael J. Caterina YR 2005 UL http://jpet.aspetjournals.org/content/314/3/1378.abstract AB 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 Ca2+ (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. The American Society for Pharmacology and Experimental Therapeutics