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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>