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Potent painkiller from spider venom antagonizes P2X3 receptors without dysgeusiaстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 5 марта 2025 г.
- Авторы: Oparin Peter, Khokhlova Oksana, Cherkashin Aleksandr, Nadezhdin Kirill, Palikov Victor, Palikova Yulia, Korolkova Yuliya, Mosharova Irina, Rogachevskaja Olga, Baranov Mikhail, Shaidullova Ksenia, Ermakova Elizaveta, Lushpa Vladislav, Bruter Alexandra, Deykin Alexey, Ivanova Elena, Silaeva Yulia, Dyachenko Igor, Bocharov Eduard, Sitdikova Guzel, Andreev-Andrievskiy Alexander, Poteryaev Dmitry, Shuster Alexander, Murashev Arkady, Kolesnikov Stanislav, Stepanenko Vasiliy, Grishin Eugene, Vassilevski Alexander
- Журнал: Molecular Therapy
- Том: 33
- Номер: 2
- Год издания: 2025
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 771
- Последняя страница: 785
- DOI: 10.1016/j.ymthe.2024.12.036
- Аннотация: P2X3 receptors are a validated molecular target in pain syndromes and chronic cough. Known P2X3 inhibitors generally suffer from poor selectivity and efficacy. Taking advantage of peptide combinatorial libraries found in venoms, we describe a P2X3 antagonist from the crab spider Thomisus onustus. This peptide potently inhibits P2X3 in the dorsal root and trigeminal ganglia neurons of rodents, as well as recombinant human P2X3, showing no effect on P2X2 or P2X2/3 receptors. PT6 presents a compact and rigid structure and produces pronounced antinociception in animal models of inflammatory and neuropathic pain at low doses (0.01–0.1 mg/kg subcutaneously). It does not show antinociceptive activity in P2rx3-knockout mice, providing further evidence in favor of its specificity. Importantly, PT6 shows no dysgeusia or ageusia effects, notoriously characteristic of small-molecule P2X3 ligands, and therefore stands out as an attractive hit for analgesic drug discovery.
- Добавил в систему: Андреев-Андриевский Александр Александрович