| Autor: |
Delgado-Ramírez Mayra, Rodriguez-Leal Fanny Junue, Rodríguez-Menchaca Aldo Azmar, Moreno-Galindo Eloy Gerardo, Sanchez-Chapula José Antonio, Ferrer Tania |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Acta Pharmaceutica, Vol 71, Iss 2, Pp 317-324 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1846-9558 |
| DOI: |
10.2478/acph-2021-0017 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
