オピオイドは,大腸筋膜のアルファ-シヌクレイン高リン酸化を誘発することで便秘を誘発する

Binghan Jia¹, Yuqiong Zhao¹, Xiaojie Ren¹

¹Department of Human Anatomy and Histoembryology, School of Basic, Medical Sciences, Ningxia Medical University, 1160 Shengli Street, 750004, Yinchuan, Ningxia Hui Autonomous Region, PR China.

Neurochemistry international

|August 20, 2025

まとめ

オピオイド誘発性便秘は,大腸におけるアルファ-シヌクレイン (α-Syn) ハイパーフォスフォリレーションを伴う. この経路を阻害することで便秘を逆転させ腸の機能を回復させることができます

科学分野:

胃腸内科
神経科学
薬理学について

背景:

オピオイド誘発性便秘 (OIC) はオピオイド治療の一般的な副作用です.
アルファ・シヌクレイン (α-Syn) は神経伝達物質のホメオスタシスに不可欠であるが,OICにおけるその役割は不明である.

研究の目的:

OICラットモデルにおける大腸不動性に対するα-Syn高リン酸化の影響を調査する.
オピオイド使用とOICを結びつける分子メカニズムの解明

主な方法:

OICのSprague-Dawleyラットモデルを使用しました.
大腸筋層のSer129 (pS129-α-Syn) で評価されたα-Syn酸化.
シナプスタンパク質と神経伝達物質合成の表現を測定した.
GSK3βとμ-オピオイド受容体 (MOR) の役割を調査した.

主要な成果:

OICラットではpS129-α-Synの発現が著しく増加した.
pS129-α-Synの抑制により,大腸不動性が逆転し,シナプスタンパク質の発現が回復しました.
オピオイドは,MOR活性化によってGSK3βを低下させ,GSK3βの活性化を高め,pS129-α-Synを誘導する.
GSK3β/pS129-α-Syn軸は,シナプス膀の密輸と神経伝達物質の放出に対するオピオイド効果を媒介する.

結論:

OICの発達は,大腸筋の神経細胞におけるα-Syn過酸化と関連している.
オピオイドは,GSK3β/α- Syn経路を通じてシナプス機能と神経伝達物質の放出を阻害することによってOICを誘発する.

キーワード:

アルファシヌクレイン大腸の運動腸内神経系 GSK3β オピオイドによる便秘 μ-オピオイド受容体

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