Doxazosin induces apoptosis of cells expressing hERG K+ channels.
Eur J Pharmacol
; 579(1-3): 98-103, 2008 Jan 28.
Article
em En
| MEDLINE
| ID: mdl-18054910
ABSTRACT
The antihypertensive drug doxazosin has been associated with an increased risk for congestive heart failure and cardiomyocyte apoptosis. Human ether-a-go-go-related gene (hERG) K(+) channels, previously shown to be blocked by doxazosin at therapeutically relevant concentrations, represent plasma membrane receptors for the antihypertensive drug. To elucidate the molecular basis for doxazosin-associated pro-apoptotic effects, cell death was studied in human embryonic kidney cells using three independent apoptosis assays. Doxazosin specifically induced apoptosis in hERG-expressing HEK cells, while untransfected control groups were insensitive to treatment with the antihypertensive agent. An unexpected biological mechanism has emerged binding of doxazosin to its novel membrane receptor, hERG, triggers apoptosis, possibly representing a broader pathophysiological mechanism in drug-induced heart failure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doxazossina
/
Apoptose
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Canais de Potássio Éter-A-Go-Go
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Anti-Hipertensivos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article