Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Body's response to spicy foods guides design of new pain relief drugs

10.06.2015

UC Davis researchers have identified the molecular interactions that allow capsaicin to activate the body's primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain. Their study appeared online June 8 in the journal Nature Chemical Biology.

Capsaicin is the ingredient that makes chili peppers spicy and hot. The same pathway in the body that responds to spicy food is also activated after injury or when the immune system mounts an inflammatory response to bacteria, viruses, or in the case of autoimmune disease, the body's own tissues.


Computer model shows how capsaicin binds with the TRPV1 receptor, causing conformational changes that lead to the sensation of pain and heat.

Courtesy of J. Zheng lab, UC Davis

'While we have known that capsaicin binds to the TRPV1 receptor with exquisite potency and selectivity, we were missing important atomic-level details about exactly how the capsaicin molecule interacts with TRPV1, one of the body's primary receptors for sensing pain and heat,' said Jie Zheng, professor of physiology and membrane biology at UC Davis and senior author on the paper.

Using computer models based on atomic force fields and existing low resolution 3-D reconstructions of the TRPV1-capsaicin complex, the researchers identified several structural areas that enable capsaicin to strongly bind to the TRPV1 receptor.

'Computational biology methods are becoming very powerful tools for predicting and ultimately validating the high-resolution structure of important biological proteins and ligands, such as capsaicin and TRPV1, when they interact,' said Vladimir Yarov-Yarovoy, assistant professor of physiology and membrane biology at UC Davis and co-author on the study.

'These tools are especially useful when the interactions are small and transient, and cannot be captured easily with high-enough resolution using traditional experimental approaches,' he said.

Fan Yang, postdoctoral fellow in the Zheng lab at UC Davis and first author on the paper, agrees.

'The electron density observed in the cryo electron microscopy structure of the TRPV1-capsaicin complex is much smaller in size compared to the chemical structure of capsaicin,' Yang said. 'With computational docking, we were able to detail the atomic interactions between capsaicin and the TRPV1 channel and later validate the molecular architecture using other experimental approaches.'

The new structural information may serve to guide the drug-design process.

'Just as we can 'get used to' a spicy dish by the end of the meal, we believe that there are ways to develop highly specific molecules that make TRPV1 less sensitive to painful stimuli,' Zheng said.

The research also explains why capsaicin does not activate the body's other channels for sensing temperature, and why the TRPV1 receptor in many other species is not activated by capsaicin. For example, birds are missing two key interaction sites, which explains why birds are insensitive to the spiciness of chili peppers.

'It is thought that the presence of capsaicin is an evolutional advantage for plants, protecting them from species that would eat the leaves while allowing birds to ingest the peppers to spread the seed,' Zheng said.

The researchers also found that sweet peppers contain a compound called capsiate, which is almost identical to capsaicin in spicy peppers but differs at one key interaction site.

'The difference is sufficient to make the sweet pepper compound bind to TRPV1 very poorly, which is probably part of the reason why it does not taste spicy,' Zheng said. 'On the Scoville pungency scale, capsaicin is 16 million, and capsiate is only 16,000.'

###

Other authors include Xian Xiao from UC Davis, Wei Cheng from Dalian Medical University, Wei Yang and Peilin Yu from the Zhejiang University, and Zhenzhen Song from the Zhejiang Sci-Tech University.

UC Davis Health System is improving lives and transforming health care by providing excellent patient care, conducting groundbreaking research, fostering innovative, interprofessional education, and creating dynamic, productive partnerships with the community. For more information, visit healthsystem.ucdavis.edu.

Carole Gan | EurekAlert!

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>