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Story ideas from the Journal of Biological Chemistry
Date:1/14/2008

COX-2 inhibitors like Celecoxib have come under scrutiny lately due to adverse cardiovascular side-effects stemming from COX-2 reduction. In both fruit fly and rat models, researchers reveal another adverse effect of Celecoxib; this drug can induce arrhythmia. More interestingly, this effect is independent of the COX-2 enzyme.

Satpal Singh and colleagues tested various Celecoxib doses on the heart rate of Drosophila, a good model for human cardiac pharmacology. To their surprise, administering 3 m Celecoxib (not much higher than the plasma levels in humans taking the drug) reduced heart rate and increased beating irregularities, while 30 m was enough to stop the heart within a minute.

The surprise arises from the fact that Drosophila do not have COX-2 enzymes. Rather, Celecoxib could directly inhibit the potassium channels that help generate the electric current that drives heartbeat.

The researchers could achieve similar heart-stopping results in rat cardiac cells, whereas aspirin, another potent COX-2 inhibitor, had no effect, confirming that another mechanism is at work. The drug also inhibited rat and human potassium channels expressed in a human cell line.

Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. They also stress it is too early to speculate on human effects, although their results suggest Drosophila are a valuable tool to investigate other COX-2 drugs.


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Contact: Nick Zagorski
nzagorski@asbmb.org
American Society for Biochemistry and Molecular Biology
Source:Eurekalert  

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