Development of new therapeutic strategy targeting interaction between RTP4-mu-delta heteromers

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19214
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: Nagasaki University
• Principal Investigator: FUJITA Wakako 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30382328)
• Research Collaborator: DEVI Lakshmi A ; UEDA Hiroshi ; YOKOTE Mini
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: RTP4 / オピオイド / 鎮痛耐性形成 / mu-delta ヘテロ二量体

Outline of Final Research Achievements

The purpose of this study is to clarify the interaction between RTP4 and mu-delta heteromer (mu-delta) and to reveal the effect of this interaction on the development of tolerance to mu opioid receptor (MOPr) signal. Here, I found long-term activation of MOPr would lead to the up-regulation of RTP4 and of the colocalization of RTP4 and mu-delta and thus results in the increase of mu-delta on cell surface. At the same time, I found the development of tolerance to Gi responses by MOPr activation. Taken together, it is hypothesized that the increase of RTP4-mu-delta interaction by long-term activation of MOPr will play an important role in development of tolerance to MOPr signal. In addition, here I could construct a deletion mutant of RTP4 that may inhibit the interaction between RTP4 and mu-delta. Moreover, I succeeded in the construction of RTP4 floxed mouse and started to breed of them. These tools will be useful for the future study to reveal this hypothesis by using in vivo study.

Free Research Field

中枢神経薬理学