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Studies on endogenous itch mediators and their interaction

内源性瘙痒介质及其相互作用的研究

基本信息

批准号：
08457635
负责人：
KURAISHI Yasushi
金额：
$ 3.52万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457635/
关键词：
itch scratching substance P histamine serotonin dynorphin somatostatin arginine

项目摘要

Although it has been claimed that antihistamines can not inhibit itch sensation of many pruritic diseases, histamine, a classical itch mediator released from mast cells, are generally considered to be a major itch mediator in the skin. In this study, to elucidate the mechanisms of itch in the skin, we examined the scratch-inducing potencies of intradermal injections of several endogenous substances that are produced in and released from primary afferent terminals, mast cells, etc. in the skin. Histamine (100 nmol/site) eliciteditch-related behavior (scratching of the injected site) in ICR mice, but not in mice of ddY,BALB/c, C57/BL,WBB6F1 +/+ or CH3/He strain. Serotonin dose-dependently elicited scratching behavior in ICR and ddY mice. Substance P,dynorphin A (1-13) and somatosatatin also produced scratching behavior, while VIP,CGRP,neurokinin A,neurokinin B,PAF and L-arginine were without apparent effects at doses examined. Scratch-inducing effects of substance P and serotonin had several features similar to those of itch in humans, suggesting scratching induced by these substances are due to an itch sensation. Scratch-inducing effect of dynorpjin A(1-13) were roughly additive to that of either substance P or somatostatin. Morphine, an opioid alkaloid known to produce itch in humans, elicited scratching following intracisterna rather than intradermal injection, findings suggesting that opioid and mu-opioid receptors are involved in itch in the central nervous systems rather than in the periphery. Although L-ariginine itself did not elicit scratching, it enhanced scratch-inducing effects of lower doses of substance P,finding suggesting that nitric oxide enhances itch of some pruritic diesase.

虽然抗组胺药不能抑制许多瘙痒性疾病的瘙痒感觉，但组胺作为肥大细胞释放的经典瘙痒介质，通常被认为是皮肤中主要的瘙痒介质。在这项研究中，为了阐明皮肤瘙痒的机制，我们检测了皮内注射几种内源性物质的致痒效力，这些物质由皮肤的初级传入终末、肥大细胞等产生和释放。组胺浓度（100 nmol/site）可引起ICR小鼠的挠痒行为，而对ddY、BALB/c、C57/BL、WBB6F1 +/+和CH3/He菌株小鼠无明显影响。血清素剂量依赖性诱导ICR和ddY小鼠抓伤行为。Substance P、dynorphin A（1-13）和somatatatin也会产生抓痕行为，而VIP、CGRP、神经激肽A、神经激肽B、PAF和l -精氨酸在检测剂量时无明显影响。P物质和5 -羟色胺的抓挠诱导作用与人类的瘙痒有几个相似的特征，这表明这些物质引起的抓挠是由于痒的感觉。dynorpjin A（1-13）的致抓作用与P物质或生长抑素的致抓作用大致相同。吗啡是一种已知能使人发痒的阿片生物碱，在内源性而非皮内注射后引起抓痒，研究结果表明阿片受体和mu-阿片受体参与中枢神经系统而非外周神经系统的瘙痒。虽然l -精氨酸本身不会引起抓挠，但它增强了低剂量P物质的抓挠诱导效果，这表明一氧化氮增强了一些瘙痒性疾病的瘙痒。