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European Journal of Pharmacology
Volume 505, Issues 1-3, 28 November 2004, Pages 229-235
 
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doi:10.1016/j.ejphar.2004.10.031    How to Cite or Link Using DOI (Opens New Window)
Copyright © 2004 Elsevier B.V. All rights reserved.

Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis

Iwao AraiCorresponding Author Contact Information, E-mail The Corresponding Author, Norikazu Takano, Yuki Hashimoto, Nobuko Futaki, Masanori Sugimoto, Nobutaka Takahashi, Tomoyuki Inoue and Shiro Nakaike

Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan

Received 5 October 2004; 
accepted 12 October 2004. 
Available online 5 November 2004.

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Abstract

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 D2, prostaglandin E1, prostaglandin E2 and prostaglandin I2 significantly suppressed the scratching, the order of inhibitory activities being prostaglandin D2much greater-thanprostaglandin I2>prostaglandin E1=prostaglandin E2. Prostaglandin D2 metabolite, prostaglandin J2 also significantly suppressed the scratching but not so 13,14-dihydro-15-keto-prostaglandin D2, and 15-deoxy-Δ12,14-prostaglandin J2. The order of the inhibitory activities of these prostaglandin D2 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-γ receptors. Likewise, topically applied arachidonic acid significantly suppressed the scratching while indomethacin enhanced it. Pretreatment of arachidonic acid increased the skin prostaglandins (prostaglandin D2, prostaglandin E2, prostaglandin F and 6-keto-prostaglandin F) contents, but indomethacin decreased the prostaglandin D2 and prostaglandin E2 contents. On the other hand, prostaglandin D2 and indomethacin had no apparent effects on histamine-induced scratching of ICR mice. These results suggested that prostaglandin D2 plays a physiological role in inhibiting pruritis of NC/Nga mice via their specific prostanoid DP1 receptors, and that prostaglandin D2 and/or a prostanoid DP1 receptor agonist may have therapeutic effects for cases of consecutive skin inflammation.

Keywords: Prostaglandin D2; Scratch; Atopic dermatitis; NC/Nga, mouse; Pruritus

Article Outline

1. Introduction
2. Materials and method
2.1. Animals
2.2. Materials
2.3. Measurement of spontaneous scratching behavior in NC/Nga mice
2.4. Measurement of histamine-induced scratching behavior in ICR mice
2.5. Measurement of skin prostaglandins contents in NC/Nga mice
2.6. Data analysis
3. Results
3.1. Effects of several prostaglandins on spontaneous scratching behavior by NC/Nga mice
3.2. Effects of prostaglandin D2 metabolites on spontaneous scratching behavior by NC/Nga mice
3.3. Effect of indomethacin on spontaneous scratching behavior by NC/Nga mice
3.4. Effect of indomethacin on the skin prostaglandins contents in NC/Nga mice
3.5. Effect of arachidonic acid on spontaneous scratching behavior by NC/Nga mice
3.6. Effect of arachidonic acid on skin prostaglandins contents in NC/Nga mice
3.7. Effect of prostaglandin D2 and indomethacin on histamine-induced scratching by ICR mice
4. Discussion
Acknowledgements
References






 
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