Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis
Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis
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DOI：
10.1016/j.ejphar.2004.10.031
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发表时间：
2004-11-28
影响因子：
5
通讯作者：
Nakaike, S
中科院分区：
文献类型：
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作者：
Arai, I;Takano, N;Nakaike, S
NC/Nga小鼠具有与人类特应性皮炎相似的病理和行为特征，并用作该疾病的模型。在常规情况下，自发和持续的抓挠是频繁的，并且可导致皮肤炎症的发作。我们研究了几种前列腺素及其相关化合物对NC/Nga小鼠抓挠行为的影响。其中，局部应用前列腺素D-2、前列腺素E-1、前列腺素E-2和前列腺素I-2对抓挠有明显的抑制作用，其抑制作用大小顺序为：前列腺素D（2）>前列腺素I-2>前列腺素E-1=前列腺素E-2。前列腺素D-2的代谢产物前列腺素J（2）也能显著抑制抓挠，但13，14-二氢-15-酮-前列腺素D-2和15-脱氧-δ（12，14）-前列腺素J（2）的抑制效果不明显。这些前列腺素D-2代谢产物的抑制活性顺序取决于前列腺素类DP 1受体的亲和力，但不取决于DP 2受体（辅助T细胞2上表达的化学引诱物受体同源分子，CRTH 2）和PPAR-gamma受体。花生四烯酸预处理可增加皮肤中前列腺素（前列腺素D-2、前列腺素E-2、前列腺素F-2 α和6-酮-前列腺素F-1 α）的含量，而吲哚美辛可降低前列腺素D-2和前列腺素E-2的含量。前列腺素D-2和吲哚美辛对组胺诱导的ICR小鼠抓挠无明显影响。这些结果表明，前列腺素D-2通过其特异性前列腺素类DP 1受体在抑制NC/Nga小鼠的皮炎中起生理作用，并且前列腺素D-2和/或前列腺素类DP 1受体激动剂可能对连续皮肤炎症的病例具有治疗作用。(C)2004 Elsevier B. V.保留所有权利。
NC/Nga mice have similar pathological and behavioral features of human atopic dermatitis and are used as a model of the disease. Under conventional circumstances, spontaneous and persistent scratching is frequent and can lead to the onset of skin inflammation. We examined the effects of several prostanoids and their related compounds on the scratching behavior of NC/Nga mice. Among them, topically applied prostaglandin D-2, prostaglandin E-1, prostaglandin E-2 and prostaglandin I-2 significantly suppressed the scratching, the order of inhibitory activities being prostaglandin D(2)much greater thanprostaglandin I-2>prostaglandin E-1=prostaglandin E-2. Prostaglandin D-2 metabolite, prostaglandin J(2) also significantly suppressed the scratching but not so 13,14-dihydro-15-keto-prostaglandin D-2, and 15-deoxy-Delta(12,14)-prostaglandin J(2). The order of the inhibitory activities of these prostaglandin D-2 metabolites depended on affinity of the prostanoid DP1 receptor but not on the DP2 receptor (chemoattractant receptor-homologous molecule expressed on T helper2 cells, CRTH2) and PPAR-gamma receptors. Likewise, topically applied arachidonic acid significantly suppressed the scratching while indomethacin enhanced it. Pretreatment of arachidonic acid increased the skin prostaglandins (prostaglandin D-2, prostaglandin E-2, prostaglandin F-2alpha and 6-keto-prostaglandin F-1alpha) contents, but indomethacin decreased the prostaglandin D-2 and prostaglandin E-2 contents. On the other hand, prostaglandin D-2 and indomethacin had no apparent effects on histamine-induced scratching of ICR mice. These results suggested that prostaglandin D-2 plays a physiological role in inhibiting pruritis of NC/Nga mice via their specific prostanoid DP1 receptors, and that prostaglandin D-2 and/or a prostanoid DP1 receptor agonist may have therapeutic effects for cases of consecutive skin inflammation. (C) 2004 Elsevier B.V. All rights reserved.