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Thallium-sensitive fluorescent assay reveals loperamide as a new inhibitor of the potassium channel Kv10.1.
Loza-Huerta, Arlet; Milo, Edgar; Picones, Arturo; Hernández-Cruz, Arturo; Luis, Enoch.
Afiliação
  • Loza-Huerta A; Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U. 04510, Mexico City, Mexico.
  • Milo E; Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U. 04510, Mexico City, Mexico.
  • Picones A; Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U. 04510, Mexico City, Mexico.
  • Hernández-Cruz A; Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U. 04510, Mexico City, Mexico.
  • Luis E; Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U. 04510, Mexico City, Mexico.
Pharmacol Rep ; 73(6): 1744-1753, 2021 Dec.
Article em En | MEDLINE | ID: mdl-34213738
BACKGROUND: Ion channels have been proposed as therapeutic targets for different types of malignancies. One of the most studied ion channels in cancer is the voltage-gated potassium channel ether-à-go-go 1 or Kv10.1. Various studies have shown that Kv10.1 expression induces the proliferation of several cancer cell lines and in vivo tumor models, while blocking or silencing inhibits proliferation. Kv10.1 is a promising target for drug discovery modulators that could be used in cancer treatment. This work aimed to screen for new Kv10.1 channel modulators using a thallium influx-based assay. METHODS: Pharmacological effects of small molecules on Kv10.1 channel activity were studied using a thallium-based fluorescent assay and patch-clamp electrophysiological recordings, both performed in HEK293 stably expressing the human Kv10.1 potassium channel. RESULTS: In thallium-sensitive fluorescent assays, we found that the small molecules loperamide and amitriptyline exert a potent inhibition on the activity of the oncogenic potassium channel Kv10.1. These results were confirmed by electrophysiological recordings, which showed that loperamide and amitriptyline decreased the amplitude of Kv10.1 currents in a dose-dependent manner. Both drugs could be promising tools for further studies. CONCLUSIONS: Thallium-sensitive fluorescent assay represents a reliable methodological tool for the primary screening of different molecules with potential activity on Kv10.1 channels or other K+ channels.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bloqueadores dos Canais de Potássio / Canais de Potássio Éter-A-Go-Go / Loperamida Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Pharmacol Rep Assunto da revista: FARMACOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: México País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bloqueadores dos Canais de Potássio / Canais de Potássio Éter-A-Go-Go / Loperamida Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Pharmacol Rep Assunto da revista: FARMACOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: México País de publicação: Suíça