• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2021 Fiscal Year Final Research Report

Dose PACAP-PAC1 receptor signaling contribute to itch transmission ?

Research Project

  • PDF
Project/Area Number 19K07324
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48030:Pharmacology-related
Research InstitutionKagoshima University

Principal Investigator

Kurihara Takashi  鹿児島大学, 医歯学域医学系, 准教授 (60282745)

Co-Investigator(Kenkyū-buntansha) 高崎 一朗  富山大学, 学術研究部工学系, 准教授 (00397176)
内田 洋平  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (30571856)
藤井 一恭  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (70452571)
Project Period (FY) 2019-04-01 – 2022-03-31
KeywordsPACAP / PAC1受容体 / PAC1受容体拮抗薬 / 非ペプチド性拮抗薬 / 脊髄痒み伝達 / PACAP欠損マウス / PAC1受容体欠損マウス
Outline of Final Research Achievements

In this study, we explored possible involvement of itch-like components in the intrathecal (i.t.) PACAP-induced aversive responses and evaluated the importance of PACAP signaling in several mouse models of itch.
The PACAP (i.t.)-evoked aversive behaviors were significantly inhibited by subcutaneous pretreatment with the μ-opioid receptor antagonist naltrexone and i.t. pretreatment of bombesin-saporin. We also found that i.t. pretreatment of PA-8, a novel small-molecule PAC1 receptor antagonist, attenuated 5-HT-induced scratching behaviors. Furthermore, single oral administration of PA-8 suppressed itch-associated behaviors in both dry skin and DNFB-induced atopic dermatitis models. In addition, the development of 5-HT and DNFB-induced itch-like behaviors was depressed in PACAP deficient mice. These results suggest that spinal PACAP/PAC1 receptor signaling is involved in in an important mechanism underlying the itch-like behaviors.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

痒みは日常的に経験する皮膚感覚の一つであるが、近年のアレルギー疾患患者の増大、さらには先進国においては人口の高齢化が著しいことから、ドライスキンに伴う痒み、腎疾患や肝疾患などの全身疾患に伴う痒み等、様々な掻痒疾患が増加することが予想される。従来の抗ヒスタミン薬、ステロイド、免疫抑制薬に加え、バイオ医薬品など重症度の高い痒み患者の一部に有効な新薬も登場しているが、高額であることに加え、依然十分な効果が得られない患者も存在している。現行の薬物とは異なる作用機序を探求する本研究は、低価格で利用可能な新しい掻痒治療薬の開発応用に寄与できると考えている。

URL: 

Published: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi