Possible involvement of 5-lipoxygenase metabolite in itch-associated response of mosquito allergy in mice.
This study investigated endogenous mediators involved in mosquito allergy-associated itching in mice. An intradermal injection of an extract of mosquito salivary gland elicited marked scratching in sensitized mice. The 5-lipoxygenase inhibitor zileuton (100 mg/kg), the 5-lipoxygenase activating peptide inhibitor MK-886 (10 mg/kg), and the glucocorticoid betamethasone 17-valerate (3 mg/kg) inhibited the scratching. The scratching was not affected by the cyclooxygenase inhibitors indomethacin and ketoprofen, the TP prostanoid receptor antagonist SQ-29548, the leukotriene B(4) antagonist ONO-4057, the cysteinyl leukotriene antagonist pranlucast, the leukotriene D(4) antagonist MK-571, the platelet-activating factor antagonist CV-3988, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester, the H(2) histamine-receptor antagonist cimetidine, the H(1) histamine-receptor antagonist terfenadine plus cimetidine, and cypoheptadine that blocks the 5-HT(1/2) serotonin receptors. Zileuton (100 mg/kg) inhibited the increased activity of the cutaneous nerve branch induced by an intradermal injection of the extract, suggesting the peripheral action. Zileuton and MK-886 (10 and 100 microM) did not affect high K(+)-induced increase in intracellular Ca(2+) concentration in cultured dorsal root ganglion neurons. The results suggest that 5-lipoxygenase metabolite(s) other than leukotriene B(4) and cysteinyl leukotrienes are involved in mosquito allergy-associated itching.
Kuraishi
Yasushi
Y
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan. kuraisy@pha.u-toyama.ac.jp
Ohtsuka
Eiji
E
Nakano
Tasuku
T
Kawai
Sanae
S
Andoh
Tsugunobu
T
Nojima
Hiroshi
H
Kamimura
Kiyoshi
K
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001624:Betamethasone Valerate / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D009033:Culicidae / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011537:Pruritus / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D011804:Quinolines / Q000494:pharmacology; D016593:Terfenadine / Q000494:pharmacology; D002722:Chlorobenzenes