Elsevier

Neuroscience

Volume 30, Issue 2, 1989, Pages 515-520
Neuroscience

Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper

https://doi.org/10.1016/0306-4522(89)90269-8Get rights and content

Abstract

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.

References (27)

  • DriedgerP.E. et al.

    Specific binding of phorbol ester tumor promoters

  • FischerS.M. et al.

    Phorbol ester induction of 8-lipoxygenase in inbred SENCAR(SSIN) but not C57BL/6J mice correlated with hyperplasia, edema, and oxidant generation but not ornithine decarboxylase induction

    Cancer Res.

    (1988)
  • GamseR.

    Capsaicin and nociception in the rat and mouse: possible role of substance P

    Naunyn-Schmiedeberg's Arch. Pharmac.

    (1982)
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      In contrast, other domains (S4–S5) of the channel have greater movement to ensure that the cation entry pore can form when activated (Liao et al., 2013) (Fig. 2). The TRPV1 channel is activated by several noxious (exogenous and endogenous) stimuli, such as high temperatures (>43 ºC) (Caterina et al., 1997; Boillat et al., 2014; Vandewauw et al., 2018), protons (pH < 5.9) (Tominaga et al., 1998), camphor (Xu et al., 2005), capsaicin (the pungent component of chili peppers) (Caterina et al., 1997), piperin, resiniferatoxin (Szallasi and Blumberg, 1989), anandamide (Zygmunt et al., 1999; Smart et al., 2000), polyamines (Ahern et al., 2006), oxytocin (Nersesyan et al., 2017), and lipoxygenase products (12-hydroxyeicosatetranoic acid, 15- hydroxy eicosatetraenoic acid) (Hwang et al., 2000). The channels are also modulated by inflammatory mediators (Chuang et al., 2001; Ma and Quirion, 2007; Zhang et al., 2008; Malek et al., 2015; Jian et al., 2016).

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