5-Iodoresiniferatoxin evokes hypothermia in mice and is a partial transient receptor potential vanilloid 1 agonist in vitro.
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 micromol/kg) evoked a hypothermic response similar to that evoked by capsaicin (9.8 micromol/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, EC(50) = 56.7 nM and 9.9 microM) that depended on Ca(2+) influx and outwardly rectifying, capsazepine-sensitive currents that were smaller than those evoked by 1 microM capsaicin. Thus, I-RTX induces TRPV1-dependent hypothermia in vivo and is a partial TRPV1 agonist in vitro.
Shimizu
Isao
I
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Iida
Tohko
T
Horiuchi
Nobuhiko
N
Caterina
Michael J
MJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced; D007473:Ion Channels / Q000819:agonists* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050916:TRPV Cation Channels
D004224:Diterpenes; D007473:Ion Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C468130:iodoresiniferatoxin; C024353:resiniferatoxin; D002211:Capsaicin; D002118:Calcium