title: Prostanoid DP1 receptor agonist inhibits the pruritic activity in NC/Nga mice with atopic dermatitis.
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 D2>>prostaglandin 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-Delta12,14-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-gamma 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 F2alpha and 6-keto-prostaglandin F1alpha) 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 pruritus 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.
authors.affiliation: Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan. i.arai@po.rd.taisho.co.jp
authors.forename: Iwao
authors.initials: I
authors.lastname: Arai
authors.forename: Norikazu
authors.initials: N
authors.lastname: Takano
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Nobuko
authors.initials: N
authors.lastname: Futaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Takahashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakaike
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000150:complications*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D011537:Pruritus / Q000209:etiology / Q000517:prevention & control*; D011982:Receptors, Prostaglandin / Q000819:agonists*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C078129:6-keto-prostaglandin F2alpha; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; C037112:9-deoxy-delta-9-prostaglandin D2; D006632:Histamine; D015237:Dinoprost; D011464:Epoprostenol; D000527:Alprostadil; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin