Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps Research study reveals new activation mechanism for pain sensing channel

24.01.2007
First-time findings describe potential new pain therapy target

The study was published January 21, 2007 in an advanced online edition of the journal Nature.

The researchers found that TRPA1, a protein that helps transmit pain signals, is a direct sensor of reactive chemicals. "While many noxious and pungent compounds were known to activate this pain receptor, we discovered that they do so by directly and irreversibly binding to the cysteine amino acids of this protein," said Ardem Patapoutian, a Scripps Research scientist whose laboratory conducted the study. "Our study shows that TRPA1 activation is directly linked to chemical insult."

"Cysteines, one of the twenty building blocks of all proteins, are known to undergo oxidation/reduction reactions," Patapoutian continued. "Somehow the TRPA1 protein is tuned to sense cysteine modifications. In fact, any cysteine reactive agent seems to activate TRPA1, although we don't know exactly how cysteine binding translates into ion channel activation."

But this activation mechanism comes with an interesting property.

"Generally, compounds that activate ion channels bind in a lock-and-key mechanism that is readily reversible," said Lindsey Macpherson, another author of the study and a Ph.D. candidate in the Scripps Research Kellogg School of Science and Technology. "The mechanism by which noxious compounds activate TRPA1 is unique. For example, compounds that activate an ion channels through a lock-and-key mechanism have structural similarity. TRPA1 activators have no structural similarity; instead, they share a common potential for chemical reactivity, and their binding is long-lasting."

TRPA1 is not unique among proteins to be activated by cysteine modifying agents, the study noted. Another signaling protein known as Kelch-like ECH-associated protein 1 (KEAP1) is activated by many of the same compounds that activate TRPA1; KEAP1 is a sensor for oxidative damage from free radicals and upregulates expression of antioxidant enzymes. Apparently, reactive compounds can activate at least two pathways through cysteine modification as a warning against cell damage, the study concluded.

"Our findings, which are the result of a successful collaboration with the Ben Cravatt and Peter Schultz labs at Scripps Research, show that modification of reactive cysteines within TRPA1 can cause channel activation," Macpherson said. "Our research efforts are now aimed at further understanding how binding of these compounds activate the channel, and identifying the physiological role of TRPA1 in sensing oxidative stress." The protein is currently being investigated by several pharmaceutical companies as a potential target for chronic pain, Patapoutian noted.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Studies and Analyses:

nachricht Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)

nachricht The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>