Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels
Terfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its anticancer properties. Lately, the subfamily 2 of inward rectifier potassium channels (Kir2) has been implicated in the progression of some tumoral...
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2021-06-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0017 |
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| author | Delgado-Ramírez Mayra Rodriguez-Leal Fanny Junue Rodríguez-Menchaca Aldo Azmar Moreno-Galindo Eloy Gerardo Sanchez-Chapula José Antonio Ferrer Tania |
| author_facet | Delgado-Ramírez Mayra Rodriguez-Leal Fanny Junue Rodríguez-Menchaca Aldo Azmar Moreno-Galindo Eloy Gerardo Sanchez-Chapula José Antonio Ferrer Tania |
| author_sort | Delgado-Ramírez Mayra |
| collection | DOAJ |
| description | Terfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its anticancer properties. Lately, the subfamily 2 of inward rectifier potassium channels (Kir2) has been implicated in the progression of some tumoral processes. Hence, we characterized the effects of terfenadine on Kir2.x channels expressed in HEK-293 cells. Terfenadine inhibited Kir2.3 channels with a strikingly greater potency (IC50 = 1.06 ± 0.11 μmol L−1) compared to Kir2.1 channels (IC50 = 27.8 ± 4.8 μmol L−1). The Kir2.3(I213L) mutant, possessing a larger affinity for phosphatidylinositol 4,5-bisphosphate (PIP2) than the wild-type Kir2.3, was less sensitive to terfenadine inhibition (IC50 = 13.0 ± 2.9 μmol L−1). Additionally, the PIP2 intracellular application had largely reduced the inhibition of Kir2.1 channels by terfenadine. Our data support that Kir2.x channels are targets of terfena-dine by affecting their interaction with PIP2, which could be regarded as a mechanism of the antitumor properties of terfenadine. |
| format | Article |
| id | doaj-art-0d31ca2c06ff461f8aa535e543861f3c |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Sciendo |
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| series | Acta Pharmaceutica |
| spelling | doaj-art-0d31ca2c06ff461f8aa535e543861f3c2025-02-02T19:57:25ZengSciendoActa Pharmaceutica1846-95582021-06-0171231732410.2478/acph-2021-0017acph-2021-0017Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channelsDelgado-Ramírez Mayra0Rodriguez-Leal Fanny Junue1Rodríguez-Menchaca Aldo Azmar2Moreno-Galindo Eloy Gerardo3Sanchez-Chapula José Antonio4Ferrer Tania5Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, MéxicoCentro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, MéxicoDepartamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, MéxicoCentro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, MéxicoCentro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, MéxicoCentro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, MéxicoTerfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its anticancer properties. Lately, the subfamily 2 of inward rectifier potassium channels (Kir2) has been implicated in the progression of some tumoral processes. Hence, we characterized the effects of terfenadine on Kir2.x channels expressed in HEK-293 cells. Terfenadine inhibited Kir2.3 channels with a strikingly greater potency (IC50 = 1.06 ± 0.11 μmol L−1) compared to Kir2.1 channels (IC50 = 27.8 ± 4.8 μmol L−1). The Kir2.3(I213L) mutant, possessing a larger affinity for phosphatidylinositol 4,5-bisphosphate (PIP2) than the wild-type Kir2.3, was less sensitive to terfenadine inhibition (IC50 = 13.0 ± 2.9 μmol L−1). Additionally, the PIP2 intracellular application had largely reduced the inhibition of Kir2.1 channels by terfenadine. Our data support that Kir2.x channels are targets of terfena-dine by affecting their interaction with PIP2, which could be regarded as a mechanism of the antitumor properties of terfenadine.https://doi.org/10.2478/acph-2021-0017terfenadineinward rectifier potassium channelsphosphatidylinositol 4,5-bisphosphatecationic amphiphilic drugs |
| spellingShingle | Delgado-Ramírez Mayra Rodriguez-Leal Fanny Junue Rodríguez-Menchaca Aldo Azmar Moreno-Galindo Eloy Gerardo Sanchez-Chapula José Antonio Ferrer Tania Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels Acta Pharmaceutica terfenadine inward rectifier potassium channels phosphatidylinositol 4,5-bisphosphate cationic amphiphilic drugs |
| title | Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels |
| title_full | Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels |
| title_fullStr | Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels |
| title_full_unstemmed | Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels |
| title_short | Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels |
| title_sort | inhibitory effect of terfenadine on kir2 1 and kir2 3 channels |
| topic | terfenadine inward rectifier potassium channels phosphatidylinositol 4,5-bisphosphate cationic amphiphilic drugs |
| url | https://doi.org/10.2478/acph-2021-0017 |
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