アトピー性皮膚炎モデルマウスの掻痒反応における末梢PACAP-PAC1受容体情報伝達系の関与

• Published in: 日本薬理学会年会要旨集 p. 3-P-224
• Main Authors: 宮田, 篤郎, 岡田, 卓哉, 中山, 智祐, 髙﨑, 一朗, 加藤, 翔, 豊岡, 尚樹, 栗原, 崇, 池田, 竜太
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: allergy; itching; neuron; skin
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-224

Previously, we demonstrated that both intradermal (i.d.) and intrathecal (i.t.) injection of PACAP (1pmol-1nmol) elicited scratching/biting behaviors in mice, and they are suppressed by pretreatment with µ-opioid receptor antagonist naltrexone. Furthermore, we showed that i.t. and i.d. PACAP-elicited scratching/biting behaviors are inhibited by co- injection of small-molecule PAC1 receptor antagonist PA-8 (1 nmol). These results suggests that both peripheral and spinal PACAP/PAC1 receptor signaling systems are involved in the transmission of itch sensations. However, it is not yet clear that PACAP/PAC1 receptor signaling systems are involved in what kind of pruritus. In this study, the importance of PACAP/PAC1 receptor signaling systems were evaluated using dinitrofluorobenzene (DNFB)-induced atopic dermatitis model mice. Repetitive application (once a week) of DNFB (1.5%) to the skin of mice elicited itch- like behaviors. Single oral administration of PA-8 (30 mg/kg) significantly suppressed DNFB-induced itch-like behaviors, suggesting the involvement of PAC1 receptors in atopic dermatitis. Application of PA-8 (0.5% in solvent ( DMSO : 100% ethanol = 1 : 9 ) ) to the skin also significantly suppressed the DNFB-induced itch-like behaviors. The result suggests that PACAP/PAC1 receptor signaling systems in the skin are involved at least in part in the itch of atopic dermatitis. Blocking peripheral PAC1 receptors may be one of the new strategies for managing itch sensations of atopic dermatitis.