The toxin targets the “wasabi receptor” and triggers a pain response, potentially allowing the study of chronic pain and inflammation.
Nearly everyone is familiar with the “wasabi receptor,” even if they have never eaten the intense Asian condiment. The TRPA1 (pronounced "trip A1") protein is embedded in sensory nerve endings throughout the body and is also responsible for causing eyes to water when exposed to fresh-cut onions.
When the wasabi receptor is activated, TRPA1 unfolds, creating a channel that allows sodium and calcium ions to flow into the cell, inducing pain and inflammation. Essentially, TRPA1 acts as a sensor for detecting chemical irritants, more specifically reactive electrophiles, that can cause significant damage to cells, such as cigarette smoke and environmental pollutants. Pungent foods may cause a reaction because they are intended to discourage animals from eating the plants that contain them.
Researchers at UC San Francisco and the University of Queensland have isolated a peptide from the venom of the Australian Black Rock scorpion that activates the wasabi receptor. They have labeled the peptide, which appears to have a defensive function because it only activates TRPA1 in mammals, the “wasabi receptor toxin" (WaTx).
WaTx was interesting to the scientists because it activates TRPA1 in an unusual manner. It possesses a unique amino acid sequence that allows the peptide to penetrate the cell membrane, something that very few proteins can do. This ability could potentially enable the delivery of drugs that typically can’t get across membranes into cells.
In the cell, WaTx binds to a site on TRPA1 known as the "allosteric nexus," the site where irritant chemicals bind. Unlike irritants, however, which modify the structure of the nexus and cause the ion channel to rapidly change from open to closed and preferentially allow entry of calcium ions, WaTx forces the channel to remain open, allowing both sodium and calcium ions to enter the cell, leading to overall high ion levels that trigger a pain response but insufficient levels of calcium to cause inflammation. The results suggest that the acute pain response can be separated from the chronic pain that results from inflammation.
Researchers hope to use WaTx to learn more about its unusual mechanism for causing a pain response and in turn about the link between chronic pain and inflammation, insights that could potentially lead to the development of new types of non-opioid pain relievers