Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resiniferatoxin is an extremely irritant diterpene present in the latex of several members of the genus Euphorbia. Its mechanism of action has been shown to be clearly distinct from that of the structurally related phorbol esters. Since resiniferatoxin possesses a 4-hydroxy-3-methoxyphenyl substituent, a key feature of capsaicin, the major pungent ingredient of plants of the genus Capsicum, we examined the ability of resiniferatoxin to induce typical capsaicin responses. We report here that treatment of rats with resiniferatoxin, like treatment with capsaicin, caused hypothermia, neurogenic inflammation, and pain. These responses were followed by loss of thermoregulation, by desensitization to neurogenic inflammation, and by chemical and thermal analgesia, with cross-tolerance between resiniferatoxin and capsaicin. Resiniferatoxin was 3 4 orders of magnitude more potent than capsaicin for the effects on thermoregulation and neurogenic inflammation. Resiniferatoxin was only comparable in potency to capsaicin, however, in the assay for induction of acute pain, and the desensitization to acute pain appeared to require less resiniferatoxin than did desensitization for the other responses. We conclude that resiniferatoxin acts as an ultrapotent capsaicin analog and hypothesize that it may distinguish between subclasses of capsaicin response.
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PMID:Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper. 274 24

When administered acutely, the vanilloid (capsaicin) receptor agonist resiniferatoxin induces marked hypothermia in the ferret, rat and mouse. The aim of this study was to further characterise the thermoregulatory effects of resiniferatoxin in the rat in an attempt to understand the mechanism by which resiniferatoxin induces this hypothermic effect. Three doses of resiniferatoxin were administered (50, 100, 200 micrograms/kg s.c.) in separate animals at an ambient temperature (Ta) of 20 degrees C but there was no apparent dose-related effect on the decrease in colonic temperature over this range. Resiniferatoxin (50 micrograms/kg s.c.) decreased whole body oxygen consumption when measured below thermoneutrality (Ta = 20 degrees C) but not at thermoneutrality (Ta = 29 degrees C); likewise there was no hypothermic response to resiniferatoxin when measured at a Ta of 29 degrees C. Operant responding for radiant heat in a cold environment (-8 degrees C) was also measured in resiniferatoxin-treated (50 micrograms/kg s.c.) rats. These experiments showed that resiniferatoxin-treated rats attempted to defend body temperature by lever pressing for more radiant heat. However, this was not sufficient to reverse the hypothermia. Two repeat doses, 1 week apart, had little or no effect on colonic temperature, oxygen consumption or operant responding in the cold. Resiniferatoxin (50 micrograms/kg s.c.) also produced hypothermia (Ta = 20 degrees C) in neonatally capsaicinized adult rats. The exact site and mode of action is still under investigation, but it is postulated that resiniferatoxin activates, and then destroys or desensitizes warm thermoreceptors.
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PMID:Thermoregulatory effects of resiniferatoxin in the rat. 785 74