Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biology of flushing could renew niacin as cholesterol drug

08.04.2009
Deft molecular detective work at Duke University Medical Center suggests that scientists may soon be able to resurrect niacin as one of the best and cheapest ways to manage cholesterol.

Niacin, also known as nicotinic acid or vitamin B3, has long been regarded as one of the most effective weapons in managing cholesterol. It can lower levels of triglycerides, fatty acids and to a lesser extent, the "bad" kind of cholesterol (LDL) while at the same time powerfully increasing the "good" kind (HDL).

But there's a catch – a big one. Patients don't like to take niacin because in most of them, it causes embarrassing, uncontrollable intense flushing, a rush of blood to the face and other skin surfaces accompanied by a prickling sensation.

Now, however, scientists have identified the discrete molecular pathways that are triggered when niacin enters the body, and they say that knowledge may lead to a revival of niacin-based treatments as therapies of choice. Their discovery appears online in the Journal of Clinical Investigation and is scheduled to appear in the journal's May 1 issue.

"This opens up whole new realms for drug discovery," says Robert Walters, M.D., a dermatologist at Duke and the lead author of the study. "Not only could it lead to new niacin-based therapies for cholesterol that patients could actually stick with, but it could also mean new treatments for flushing that comes with some types of allergic reactions, hives and other disorders."

The discovery builds upon a growing body of knowledge at Duke about G protein coupled receptors, molecules that dot cell surfaces throughout the body and manage its response to drugs, hormones, pain, growth factors and many other incoming chemical signals. Robert Lefkowitz, M.D., a Howard Hughes Medical Institute investigator at Duke and the senior author of the study, was the first to identify these receptors and some of the roles they play in health and well-being.

Working together, Lefkowitz and Walters conducted various laboratory and animal experiments to track exactly what happens when niacin enters the body. Earlier, others had found that it first activates a specific G protein coupled receptor known as GP109A. This receptor, in turn, alerts other sets of proteins, including G proteins and a group referred to as beta-arrestins. One particular protein in that group, beta-arrestin1, was found to trigger the chemical reaction that led to flushing.

"Niacin stimulates production of a vasodilator that dramatically increases blood flow to the face, causing the flush and the hot, prickly sensation – and beta-arrestin1 is the culprit that enables that to happen," says Walters. "Interestingly, however, beta-arrestin1 plays no role whatsoever in niacin's ability to lower cholesterol and fatty acids. The G proteins do that."

The finding reinforces some of Lefkowitz's recent research that demonstrated that beta-arrestins, which often work in tandem with G proteins, can sometimes work independently of them, initiating their own signals.

Lefkowitz says the discovery opens the door to the possibility of developing a "biased ligand," a drug that would trigger GP109A, but not the beta-arrestins. "That might give us a way to keep all the lipid-modifying benefits of niacin, but isolate its downside," he said.

That might not be as simple as it sounds, however. Other studies suggest that enhancing niacin's ability to boost HDL may be more complex than what appears at, well, first blush.

"GPR109A receptors are most often found in fat, the spleen , adrenal glands and lungs – they are absent from the liver and intestines, where most HDL is made and metabolized, so there may well be other mechanisms of action for the beneficial effects of niacin in addition to those performed by GPR109A," says Lefkowitz.

Lefkowitz is a scientific founder of Trevena, a company that is developing G protein coupled receptor-targeted drugs.

The study was funded by the National Institutes of Health, the Howard Hughes Medical Institute and a Dermatology Foundation Physician Scientists Career Development Award to Dr. Walters.

Colleagues from Duke who contributed to the study include Arun Shukla, Jeffrey Kovacs, Christopher Lam and Erin Whalen, from the department of medicine, Jonathan Violin, from the department of biochemistry, Scott DeWire and J. Ruthie Chen, from the Howard Hughes Medical Institute and Michael Muehlbauer, from the Sarah W. Stedman Nutrition and Metabolism Center.

Michelle Gailiun | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Fungi that evolved to eat wood offer new biomass conversion tool
25.07.2017 | University of Massachusetts at Amherst

nachricht New map may lead to drug development for complex brain disorders, USC researcher says
25.07.2017 | University of Southern California

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA flights gauge summer sea ice melt in the Arctic

25.07.2017 | Earth Sciences

Fungi that evolved to eat wood offer new biomass conversion tool

25.07.2017 | Life Sciences

New map may lead to drug development for complex brain disorders, USC researcher says

25.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>