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Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807167

RESUMO

Atractylodin (ATR) is a bioactive component found in dried rhizomes of Atractylodes lancea (AL) De Candolle. Although AL has accumulated empirical evidence for the treatment of pain, the molecular mechanism underlying the anti-pain effect of ATR remains unclear. In this study, we found that ATR increases transient receptor potential ankyrin-1 (TRPA1) single-channel activity in hTRPA1 expressing HEK293 cells. A bath application of ATR produced a long-lasting calcium response, and the response was completely diminished in the dorsal root ganglion neurons of TRPA1 knockout mice. Intraplantar injection of ATR evoked moderate and prolonged nociceptive behavior compared to the injection of allyl isothiocyanate (AITC). Systemic application of ATR inhibited AITC-induced nociceptive responses in a dose-dependent manner. Co-application of ATR and QX-314 increased the noxious heat threshold compared with AITC in vivo. Collectively, we concluded that ATR is a unique agonist of TRPA1 channels, which produces long-lasting channel activation. Our results indicated ATR-mediated anti-nociceptive effect through the desensitization of TRPA1-expressing nociceptors.


Assuntos
Furanos/metabolismo , Furanos/farmacologia , Canal de Cátion TRPA1/metabolismo , Analgésicos/metabolismo , Analgésicos/farmacologia , Animais , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Gânglios Espinais/metabolismo , Células HEK293 , Humanos , Isotiocianatos/farmacologia , Lidocaína/análogos & derivados , Lidocaína/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Nociceptividade/efeitos dos fármacos , Nociceptores/metabolismo , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Canal de Cátion TRPA1/agonistas , Canal de Cátion TRPA1/efeitos dos fármacos , Canais de Cátion TRPC/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo
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