Control of itch by topical application of cholecystokinin and its use for novel therapy

局部应用胆囊收缩素控制瘙痒及其在新疗法中的应用

• 批准号: 22659208
• 负责人: TOKURA Yoshiki
• 金额: $ 2.02万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659208/
• 关键词: コレシストキニン; かゆみ; 神経ペプチド; 肥満細胞; 角化細胞; 血管内皮細胞; サブスタンスP; CCK2R; そう痒治療薬

Cholecystokinin(CCK) serves as a gastrointestinal hormone and also functions as a neuropeptide in central nervous system(CNS). CCK may be a downregulator in CNS as represented by its anti-opioid properties. The existence of CCK in peripheral nervous system has also been reported. We investigated the suppressive effects of various CCKs on the peripheral pruritus in mice. ICR mice were painted with CCK synthetic peptides on the clipped back and injected intradermally with substance P(SP) on the same site. The frequency of SP-induced scratch was reduced significantly by topical application of sulfated CCK8(CCK8S) and CCK7(CCK7S), but not by non-sulfated CCK8, CCK7 or CCK6. Dermal injection of CCK8S also depressed the scratch frequency, suggesting that dermal cells as well as epidermal keratinocytes are the targets of CCKs. By real-time PCR, mRNA for CCK2R, one of the two types of CCK receptors, was expressed highly in mouse fetal skin-derived mast cells(FSMCs) and moderately ICR mouse keratinocytes. CCK8S decreased in vitro compound 48/80-promoted degranulation of FSMCs with a transient elevation of the intracellular calcium concentration. These findings suggest that CCK exerts an anti-pruritic effect mainly via mast cells, and topical CCK may be clinically useful for pruritic skin disorders.

CCK既是一种胃肠激素，又是中枢神经系统(CNS)的神经肽。CCK可能是中枢神经系统的一种下行调节因子，其抗阿片类物质的作用以此为代表。也有报道称CCK存在于外周神经系统。我们研究了不同CCK对小鼠外周皮肤瘙痒的抑制作用。将CCK合成肽涂抹于ICR小鼠背部，皮内注射P物质(SP)。局部应用硫酸化CCK8(CCK8S)和CCK7(CCK7S)可显著降低SP引起的划痕频率，但不能减少非硫酸盐化CCK8、CCK7或CCK6引起的划痕。皮肤注射CCK8S也可降低划痕频率，提示真皮细胞和表皮角质形成细胞是CCKs的作用靶点。实时定量聚合酶链式反应显示，CCK受体CCK2R在小鼠胎儿皮肤肥大细胞(FSMCs)和中度ICR小鼠角质形成细胞中高表达。CCK8S可抑制化合物48/80促进的FSMC脱颗粒，并使细胞内钙离子浓度一过性升高。这些发现表明，CCK主要通过肥大细胞发挥止痒作用，局部应用CCK可能对瘙痒皮肤病有临床应用价值。

项目成果

Spicular form titanium dioxide induces IL-1 alpha/beta production of keratinocytes

针状二氧化钛诱导角质形成细胞产生 IL-1 α/β

• 发表时间: 2010
• 作者: Kobayashi M;Sakabe J;Nakamura M;Tokura Y
• 通讯作者: Tokura Y

Angiolymphoid hyperplasia with eosinophilia occurring on the penis : case report and literature review.

阴茎上发生血管淋巴样增生伴嗜酸性粒细胞增多：病例报告和文献综述。

• 发表时间: 2010
• 作者: Ohmori S;Sugita K;Sawada Y;Hino R;Nakamura M;Tokura Y
• 通讯作者: Tokura Y

アトピー性皮膚炎:バリア異常とアレルギー

特应性皮炎：屏障异常和过敏

• 发表时间: 2010
• 作者: 吉村耕一;青木浩樹;戸倉新樹
• 通讯作者: 戸倉新樹

抗ヒスタミン薬の今日的話題を問う

询问有关抗组胺药的当前话题

• 发表时间: 2010
• 作者: Kiyono Y;et al.;戸倉新樹
• 通讯作者: 戸倉新樹

アトピー性皮膚炎に対するタクロリムス軟膏の使用経験-全身への外用療法による皮疹とQOLの改善-

他克莫司软膏治疗特应性皮炎的经验 - 通过全身局部治疗改善皮疹和生活质量 -

• 发表时间: 2011
• 期刊: Progress in Medicine
• 作者: 伊豆邦夫;森智子;戸倉新樹
• 通讯作者: 戸倉新樹