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New nitric oxide test has medical implications

MIT researchers have developed a means to detect nitric oxide that could help improve scientists' understanding of this molecule's role in neurological signaling and other biological functions.

Professor Stephen Lippard (head of the Department of Chemistry), postdoctoral fellow Katherine J. Franz and chemistry senior Nisha Singh synthesized a nitric oxide sensing system that consists of a molecule whose fluorescence switches on when nitric oxide is present. They reported their findings in the June 16 international edition of the German publication Angewande Chemie.

Nitric oxide plays a major role in the regulation of blood pressure, the prevention of blood clotting, the dilation of blood vessels and the destruction of pathogens. It is used extensively in medical treatment; for example, nitroglycerin ameliorates the pain of angina by supplying nitric oxide to the blood vessels that supply the heart. The popular drug Viagra controls penile erection by regulating nitric oxide.

To understand the mechanism of nitric oxide's action in the body, medical researchers needed a sensitive means of detecting the molecule in vivo. An effective sensor system had to be sensitive only to nitric oxide, even in the presence of other chemically active molecules such as oxygen, and able to measure the minute concentrations normally found in living cells.

The new sensor consists of a central cobalt atom surrounded by two organic "arms." In the absence of nitric oxide, the molecule fluoresces only very weakly. When nitric oxide is present, it chemically bonds to the cobalt atom, causing a molecular rearrangement that results in a substantial, measurable increase in fluorescence. This indicator does not respond to other molecules, such as oxygen.

"Many of the nitric oxide detectors used today are based on identification of its decomposition products, nitrite and nitrate," said Professor Lippard. "In contrast, our fluorescence indicator reacts directly with nitric oxide. It has the potential to track the formation of nitric oxide in real time."

The scientists are now working on the development of more sensitive, water-soluble sensors with a stronger fluorescence response. "With this future generation of sensors it should be possible to measure nitric oxide in cell cultures. In the distant future, applications to understand nitric oxide-triggered neurobiological events in living organisms, and possibly even medical applications, could emerge," Professor Lippard said.

The work was supported by the National Science Foundation. Professor Lippard has also received a two-year, $200,000 Technological Innovations in Neuroscience Award from the McKnight Endowment Fund for Neuroscience for his work.

A version of this article appeared in MIT Tech Talk on July 12, 2000.

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