Acta Pharmaceutica, Vol. 71 No. 2, 2021.
Short communication, Note
https://doi.org/10.2478/acph-2021-0017
Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels
MAYRA DELGADO-RAMÍREZ
; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, México
FANNY JUNUE RODRIGUEZ-LEAL
; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, México
ALDO AZMAR RODRÍGUEZ-MENCHACA
; Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, México
ELOY GERARDO MORENO-GALINDO
; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, México
JOSÉ ANTONIO SANCHEZ-CHAPULA
; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, México
TANIA FERRER
; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, COL 28045, México
Abstract
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 terfenadine by affecting their interaction with PIP2, which could be regarded as a mechanism of the antitumor properties of terfenadine.
Keywords
terfenadine; inward rectifier potassium channels; phosphatidylinositol 4,5-bisphosphate; cationic amphiphilic drugs
Hrčak ID:
241050
URI
Publication date:
30.6.2021.
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