New inhibitory effects of cilnidipine on microglial p2x7 receptors and il-1β release: An involvement in its alleviating effect on neuropathic pain

Tomohiro Yamashita, Sawako Kamikaseda, Aya Tanaka, Hidetoshi Tozaki-Saitoh, Jose M.M. Caaveiro, Kazuhide Inoue, Makoto Tsuda

研究成果: ジャーナルへの寄稿学術誌査読

3 被引用数 (Scopus)

抄録

P2X7 receptors (P2X7Rs) belong to a family of ATP-gated non-selective cation channels. Microglia represent a major cell type expressing P2X7Rs. The activation of microglial P2X7Rs causes the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β). This response has been implicated in neuroinflammatory states in the central nervous system and in various diseases, in-cluding neuropathic pain. Thus, P2X7R may represent a potential therapeutic target. In the present study, we screened a chemical library of clinically approved drugs (1,979 compounds) by high-throughput screening and showed that the Ca2+ channel blocker cilnidipine has an inhibitory effect on rodent and human P2X7R. In primary cultured rat microglial cells, cilnidipine inhibited P2X7R-mediated Ca2+ responses and IL-1β release. Moreover, in a rat model of neuropathic pain, the intrathecal administration of cilnidipine produced a reversal of nerve injury-induced mechanical hy-persensitivity, a cardinal symptom of neuropathic pain. These results point to a new inhibitory effect of cilnidipine on microglial P2X7R-mediated inflammatory responses and neuropathic pain, proposing its therapeutic potential.

本文言語英語
論文番号434
ページ(範囲)1-13
ページ数13
ジャーナルCells
10
2
DOI
出版ステータス出版済み - 2月 2021

!!!All Science Journal Classification (ASJC) codes

  • 医学(全般)

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