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 Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>