Discovery of itch receptors in throats of mice could one day lead to better asthma treatments

Working with mice, Johns Hopkins researchers report they have found that itch receptors previously discovered in skin are also present in the airways and that, when activated, these receptors appear to contribute to airway constriction and hypersensitivity, hallmarks of asthma and other respiratory disorders. If the same process is active in people, the researchers say, the receptors may be a promising new target for the development of drug therapies.

In a report on the study, published Feb. 5 in Nature Neuroscience, researchers say the biochemical receptor—known as a G protein-coupled receptor—was present on nerve cells in the lower respiratory tracts of lab mice.

"The findings give us a fuller picture of what airway reactivity looks like," says Xinzhong Dong, professor of neuroscience at the Johns Hopkins University School of Medicine.

Dong said he and his team were inspired to study "itchiness" in the airway by asthma patients who reported the sensation in their lungs just prior to full-blown asthma symptoms such as wheezing. Though he has been studying the G protein-coupled receptor on the skin for many years, Dong said he had not yet looked for it in other parts of the body.

Using fluorescent antibodies designed specifically to light up the receptor in mice, the investigators observed it on vagus nerves, which serve as a main biochemical connection between airway cells and the brain.

To explore the effects of the receptor on the airway, the researchers used an itch activator that specifically targets the G protein-coupled receptor to induce a reaction. They found that mice with the G protein-coupled receptor breathed more quickly and with more effort after exposure to the activator than mice lacking it, evidence that the receptors are activated before an asthma-like attack.

Currently, asthma treatments such as anticholinergics target the hypersensitive nerves that connect the brain to so-called parasympathetic neurons in the smooth muscle of the airway.

"We know that influenza stresses the respiratory system in humans," Dong says. "Through this test, we saw that in mice, activating our receptor made the reaction much, much worse."

In the future, Dong hopes to identify a compound that can block the G protein-coupled receptor on vagus nerves as a means of stopping airway "itch" and curbing asthma.

Other researchers involved in this study include Liang Han, Nathachit Limjunyawong, Zhe Li, Fei Ru, Marian Kollarik, Bradley J. Undem, and Brendan J. Canning of the Johns Hopkins University School of Medicine; Olivia J. Hall and Wayne Mitzner of the Johns Hopkins Bloomberg School of Public Health; and Haley Steele, Yuyan Zhu, and Julie Wilson of the Georgia Institute of Technology.