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Nitric oxide: Key to cardiovascular and pulmonary function and drug effectiveness

A naturally occurring molecule in the body appears to control whether certain medications, such as beta adrenergic receptor agonists used in acute heart failure or in inhalers for asthma, lose their effectiveness over time.

Nitric oxide is a molecule produced by the body that controls many functions, including the contraction or dilation of blood vessels.

New experiments conducted by Duke University Medical Center and Howard Hughes Medical Institute researchers have shown that specialized forms of nitric oxide called SNOs may be the key to a problem that has stumped physicians for years -- why specific drugs for such diseases as heart failure or asthma lose their effectiveness over time.

Almost half of all drugs on the market today, as well as many hormone and neurotransmitters, target a specific family of cell surface receptors known as G-protein coupled receptors. The researchers believe that the presence or absence of nitric oxide or SNOs determines whether these receptors continue to function properly. This action is controlled by the ability of nitric oxide to inhibit a key regulatory system which ordinarily shuts the receptors off after they are stimulated

The researchers reported their latest findings on Friday, May 4, in the journal Cell.

"This work is significant in that it demonstrates how two of the most pervasive physiological systems -- G-protein coupled receptors and nitric oxide -- come together to influence one another," said Erin Whalen, Ph.D., who spent six years focusing on the link between the two biological systems. Whalen is a postdoctoral fellow in the laboratory of Robert Lefkowitz, M.D., a Howard Hughes Medical Institute investigator at Duke who first cloned these receptors in 1986. The link was cemented through a collaboration with Matt Foster, a post-doctoral fellow in the laboratory of Jonathan Stamler M.D.

G-protein coupled receptors reside on the cell surface where they interact
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Source:Duke University Medical Center


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