Back to Search
Start Over
Doxazosin induces apoptosis of cells expressing hERG K+ channels.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2008 Jan 28; Vol. 579 (1-3), pp. 98-103. Date of Electronic Publication: 2007 Dec 04. - Publication Year :
- 2008
-
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.
- Subjects :
- Adrenergic alpha-Antagonists pharmacology
Cell Line
Electrophysiology
Ether-A-Go-Go Potassium Channels metabolism
Flow Cytometry
Humans
In Situ Nick-End Labeling
Staining and Labeling
Antihypertensive Agents pharmacology
Apoptosis drug effects
Doxazosin pharmacology
Ether-A-Go-Go Potassium Channels drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 579
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18054910
- Full Text :
- https://doi.org/10.1016/j.ejphar.2007.10.051