12(S)-HPETE induces itch-associated scratchings in mice

doi:10.1016/j.ejphar.2006.09.057

European Journal of Pharmacology

Volume 554, Issue 1, 5 January 2007, Pages 30-33

https://doi.org/10.1016/j.ejphar.2006.09.057 Get rights and content

Abstract

The itch-associated responses evoked by intradermal injection of 12(S)-HPETE and leukotriene B₄ were compared in ICR-mice. 12(S)-HPETE and leukotriene B₄ (0.01–0.2 nmol/site) induced scratching of the injected site, respectively; the dose-responses were a peak at 0.05 nmol/site (12(S)-HPETE) or 0.03 nmol/site (leukotriene B₄). The scratching response by 12(S)-HPETE (0.05 nmol/site) started within 1 min, peaked in the first 10 min period, had almost subsided by 25 min whereas the effect of leukotriene B₄ peaked in the second 10 min. The effect of leukotriene B₄ is slightly stronger than that of 12(S)-HPETE in 40 min of count. The scratching induced by 12(S)-HPETE was inhibited by capsaicin, naltrexon, and LY255283. These results suggest the possibility that 12-lipoxygenase product can be added to a new member of an endogenous itch mediator in the skin.

Introduction

Pruritis (itching) can be defined subjectively as a poorly localized, non-adapting, usually unpleasant sensation that provokes a desire to scratch (Weisshaar et al., 2003). This sensation accompanies various skin diseases (e.g. atopic dermatitis, contact dermatitis, and urticaria) and several systemic disorders (e.g. chronic renal failure and cholestasis) (Wahlgren, 1991, Andoh et al., 2001). The details of mechanisms and endogenous mediators of itching are still unclear. Many endogenous chemicals, such as amines, proteases, growth factors, neuropeptides, opioids, cytokines and eicosanoids, are locally pruritogenic when injected into the skin. With regard to lipoxygenase products, the level of leukotriene B₄ was reported to increase in the skin of pruritus patients (Brain et al., 1984, Ruzicka et al., 1986). Intradermal injection of leukotriene B₄ elicits apparent itching-associated response in mice (Andoh and Kuraishi, 1998) and humans (Camp et al., 1983). Leukotriene D₄ and leukotriene C₄ are not pruritogenic after intradermal injection in human subjects (Camp et al., 1983).

In an effort to find a new pruritogen in animal models, we tested the possibility that products of other lipoxygenases (12-, or 15-), not 5-lipoxygenase, could be pruritogens.

Here, we report the case of 12(S)-HPETE as a possible pruritogen to evoke an itching in animal models (Andoh and Kuraishi, 1998).

Section snippets

Materials

Leukotriene B₄, 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), one of products of 12-lipoxygenase, LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, Souza et al., 2000) and U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, Falcone and Aharony, 1990) were purchased from BIOMOL. The ethanol stocks of leukotriene B₄, 12(S)-HPETE, LY255283, and U75302 were dissolved in physiological saline. These reagents were

Time-course of scratching behavior by 12(S)-HPETE and leukotriene B₄

Fig. 1A and B show the time-course of scratching behavior for 40 min after the injection of 12(S)-HPETE (0.03 nmol/site) and leukotriene B₄ (0.03 nmol/site), respectively. Scratching was first observed within 1 min after injection in all mice examined and then appeared intermittently. The scratching behavior diminished substantially by 25 min in our experiments.

Dose–response curve of 12(S)-HPETE and leukotriene B₄

Fig. 2A and B show that both 12(S)-HPETE and leukotriene B₄ elicited significant scratching at intradermal doses of 0.01–0.2 nmol/site,

Discussion

Products of lipoxygenases are implicated in skin physiology and pathology (Ziboh et al., 2002). In a recent study of pruritus, leukotriene B₄, a 5-lipoxygenase metabolite of arachidonic acid, was discovered as a new pruritogen in mice acting at low dose (Andoh and Kuraishi, 1998). However, other lipoxygenase metabolites of arachidoic acid were not fully studied for their pruritogenic activities. We tested the products of other lipoxygenases, 5-lipoxygenase, as possible pruritogens. We found

Acknowledgements

The authors are very grateful to Jung Jin Sang for the help of injection of 12(S)-HPETE and leukotriene B₄. This study was supported in part by the National Research Laboratory Program (2005-01319), NRDP, Ministry of Science and Technology, Republic of Korea.

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Short communication12(S)-HPETE induces itch-associated scratchings in mice

Abstract

Introduction

Section snippets

Materials

Time-course of scratching behavior by 12(S)-HPETE and leukotriene B4

Dose–response curve of 12(S)-HPETE and leukotriene B4

Discussion

Acknowledgements

Eur. J. Pharmacol.

Brain Res. Mol. Brain Res.

J. Invest. Dermatol.

J. Biol. Chem.

Eur. J. Pharmacol.

J. Invest. Dermatol.

Eur. J. Pharmacol.

Prostaglandins Leukot. Essent. Fat. Acids

J. Biol. Chem.

Short communication
12(S)-HPETE induces itch-associated scratchings in mice

Time-course of scratching behavior by 12(S)-HPETE and leukotriene B₄

Dose–response curve of 12(S)-HPETE and leukotriene B₄