Pharmacological characterization of itch-associated response induced by repeated application of oxazolone in mice.
We investigated pharmacological characteristics of the itch-associated response to chronic dermatitis induced by 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone) repeated application in mice. Application of an oxazolone challenge to mice with oxazolone-induced chronic dermatitis evoked severe and transient scratching behavior for up to 1h. Thereafter, mild and continuous scratching behavior was observed for at least 8 h. Both severe and continuous scratching behaviors were suppressed by the opioid-receptor antagonist naltrexone, but not by the H(1) histamine-receptor antagonist fexofenadine, 5-hydroxytryptamine-2 (5-HT(2))-receptor antagonist methysergide, NK(1)-receptor antagonist LY303870, cyclooxygenase inhibitor indomethacin, or the platelet-activating factor-receptor antagonist YM264. The severe scratching behavior was suppressed by the 5-lipoxygenase inhibitor zileuton and leukotriene B(4)-receptor antagonist ONO-4057, but not by the cysteinyl leukotriene-receptor antagonist montelukast. The continuous scratching behavior was suppressed by pretreatment with the non-selective muscarinic acetylcholine-receptor antagonist atropine and M(3) muscarinic acetylcholine-receptor antagonist darifenacin. These results suggest that leukotriene B(4) receptor and M(3) muscarinic acetylcholine receptor are involved in the itch-associated response induced by repeated application of oxazolone in mice.
Tsukumo
Yukihito
Y
Pharmacological Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Nagaizumi-cho, Shizuoka, Japan. yukihito.tsukumo@kyowa-kirin.co.jp
Harada
Daisuke
D
Manabe
Haruhiko
H
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000982:Antipruritics / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D010081:Oxazolone / Q000008:administration & dosage / Q000276:immunology; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D018926:Anti-Allergic Agents; D000982:Antipruritics; D006241:Haptens; D020024:Leukotriene Antagonists; D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D018102:Receptors, Leukotriene B4; D010081:Oxazolone