The human body's response to spicy food guide the design of a new type of pain killer
At the University of California, Davis researchers identify a can let capsaicin activation of molecular interactions of physical sensations of heat and pain is the major receptor, which for the design of a more selectivity and effectiveness of analgesics paved the way. Their research was published online in June 8th in the Journal Chemical Biology Nature.
Capsaicin is to allow the red pepper spicy ingredients. The body of spicy food make a response with a path also being injured or immune system to bacteria, viruses, initiate an inflammatory response, or in the autoimmune disease of the body's own tissues initiated activation of inflammatory response.
"Although we already know that the capsaicin and TRPV1 receptor binding with strong ability and selectivity, but we don't know at the atomic level capsaicin how to interact with the TRPV1 important details, TRPV1 is human feelings of pain and heat of one of the major receptors," the University of California, Davis physiology and membrane biology professor, the study's senior author Jie Zheng said.
Using a computer model of the atom force field and the existing of complex of TRPV1- capsaicin of low resolution 3-D reconstruction based on, the researchers identified the to capsaicin strongly with the TRPV1 receptor binding of several regional structure.
"Methods in computational biology is becoming a very powerful tool, used to predict and verify the final such as capsaicin, TRPV1 and other important biological protein and ligand in the interaction between their high resolution structure," physiology, University of California, Davis science and membrane biology, help, and the study co-author Vladimir Yarov-Yarovoy said. "These tools are particularly useful when these interactions are small and fleeting, and can not be easily captured with high resolution in traditional experimental methods."
Fan, a postdoctoral researcher at the University of California at Davis's Zheng lab, and the paper's first author, Yang, agrees.
"Compared with the chemical structure of capsaicin, the electron density scales observed in the low-temperature electron microscopic structures of the TRPV1- capsaicin complex are far smaller," Yang said. "With the method of calculating molecular docking, we have the ability to obtain the details of the atomic interaction between capsaicin and TRPV1 channels, and then use other experimental methods to verify this molecular architecture."
This new structural information may be used to guide the drug design process, the team said.
"As we can 'get used to' spicy food when we're eating, we believe there's a way to develop highly specific molecules that can make TRPV1 less sensitive to pain stimuli," Zheng said.
This study also explains why capsaicin does not activate other channels in the body for sensory temperature, as well as why many other species of TRPV1 receptors have not been activated by capsaicin. Birds, for example, lack two key interactions, which explains why birds are not sensitive to red chili peppers.
"It is believed that the presence of capsaicin is an evolutionary advantage of plants, protecting them from the damage of leaf eating species, while allowing the birds to eat pepper to spread their seeds," Zheng said.
The researchers also found that green peppers contain a called capsinoid compound and its capsaicin and capsanthin is almost the same, but there is a key interaction in different parts of.
"The difference is enough to make the green pepper compounds and TRPV1 with very poor, which may is it tastes spicy, not part of the reason," Zheng said. In accordance with the "Scoville pungency, 1600 000 is capsaicin and Capsinoids by only 16000 degrees."
Other authors of the study include from the University of California, Davis Xian Xiao, from Dalian Medical University in China Wei Chen, from Zhejiang University in China Wei Yang and Peilin Yu, and from Zhejiang Sci tech Zhenzhen song.
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