Kuraishi Yasushi, Ohtsuka Eiji, Nakano Tasuku, Kawai Sanae, Andoh Tsugunobu, Nojima Hiroshi, Kamimura Kiyoshi
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
J Pharmacol Sci. 2007 Sep;105(1):41-7. doi: 10.1254/jphs.fp0070404. Epub 2007 Sep 8.
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.
本研究调查了参与小鼠蚊虫过敏相关瘙痒的内源性介质。皮内注射蚊唾液腺提取物可引起致敏小鼠明显的搔抓行为。5-脂氧合酶抑制剂齐留通（100mg/kg）、5-脂氧合酶激活肽抑制剂MK-886（10mg/kg）和糖皮质激素倍他米松17-戊酸酯（3mg/kg）可抑制搔抓行为。搔抓行为不受环氧化酶抑制剂吲哚美辛和酮洛芬、TP前列腺素受体拮抗剂SQ-29548、白三烯B4拮抗剂ONO-4057、半胱氨酰白三烯拮抗剂普仑司特、白三烯D4拮抗剂MK-571、血小板活化因子拮抗剂CV-3988、一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸甲酯、H2组胺受体拮抗剂西咪替丁、H1组胺受体拮抗剂特非那定加西咪替丁以及阻断5-HT(1/2)5-羟色胺受体的赛庚啶的影响。齐留通（100mg/kg）可抑制皮内注射提取物诱导的皮神经分支活性增加，提示其具有外周作用。齐留通和MK-886（10和100μM）不影响高钾诱导的培养背根神经节神经元细胞内钙浓度升高。结果表明，除白三烯B4和半胱氨酰白三烯外，5-脂氧合酶代谢产物参与了蚊虫过敏相关瘙痒。
