Animal study reveals a skin itch receptor contributes to airway constriction

March 9, 2018, Johns Hopkins University
The researchers 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. Credit: iStock

Working with mice, Johns Hopkins researchers report they have found previously known skin itch receptors in the airways that appear to contribute to bronchoconstriction and airway hypersensitivity, hallmarks of asthma and other respiratory disorders. The investigators' experiments in mice suggest that the receptors' activation directly aggravates airway constriction and—if the same process is active in people—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 reactivity looks like," says Xinzhong Dong, Ph.D., professor of neuroscience at the Johns Hopkins University School of Medicine Institute for Basic Biomedical Sciences.

Dong said he and his team were inspired to study "itchiness" in the airway by 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 and the brain.

To explore the effects of the receptor on the airway, the researchers used a protein called BAM8-22, which is 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 receptor activator than mice lacking it, evidence that the 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.

To investigate what, if any, role vagus neurons have in this system, Dong and his team repeated the experiments, while also activating the airway smooth muscles using acetylcholine—a neurotransmitter used throughout the nervous system to activate muscles. They found that stimulation of the G protein-coupled receptor increased airway constriction more than activating the airway smooth muscles alone.

The research team then infected specially bred mice carrying G and those without the receptor with an influenza virus—which is known to trigger asthma attacks in humans. When the researchers then administered acetylcholine to the mice through the nebulizer, they observed that mice with the G protein-coupled receptors reacted more vigorously than those with only smooth muscle reactions, and they also showed increased airway restriction compared to their counterparts without the receptor.

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

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.

Explore further: Researchers discover receptor that protects against allergies, asthma

More information: Liang Han et al. Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0074-8

Related Stories

Researchers discover receptor that protects against allergies, asthma

February 26, 2018
A special receptor on cells that line the sinuses, throat and lungs evolved to protect mammals from developing a range of allergies and asthma, according to a study from researchers at Johns Hopkins Bloomberg School of Public ...

New molecular target could help ease asthma

March 7, 2018
Researchers at UC Davis Health and Albany Medical College have shown that the protein vascular endothelial growth factor A—or VEGFA—plays a major role in the inflammation and airway obstruction associated with asthma.

New drug therapy could lead to more effective treatment for millions with asthma

February 7, 2018
Rutgers New Jersey Medical School researchers identified a new treatment that could lead to more effective drug therapy for millions of individuals with asthma and other respiratory disorders such as chronic obstruction pulmonary ...

Research team learns more about why airway closes up during asthma attacks

October 16, 2014
The molecular regulation of smooth-muscle contraction is an important determinant of airway responses during an acute asthmatic attack. In acute asthma, various triggers, including viral illnesses and aeroallergens, can cause ...

Study reveals nervous system's role in asthma attacks

July 22, 2014
(Medical Xpress)—Asthma is a debilitating condition that kills 250,000 people around the world each year. People with asthma have hyperreactive airways and thickened lung walls obstructed with mucus. During an asthma attack, ...

Receptor dynamics provide new potential for pharmaceutical developments

August 10, 2017
The dynamics among certain so-called G protein-coupled receptors, of vital importance for the function of cells in the body, are different than previously believed. This has been reported by researchers from Karolinska Institutet ...

Recommended for you

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful

November 14, 2018
Expect a shot to hurt and it probably will, even if the needle poke isn't really so painful. Brace for a second shot and you'll likely flinch again, even though—second time around—you should know better.

A 15-minute scan could help diagnose brain damage in newborns

November 14, 2018
A 15-minute scan could help diagnose brain damage in babies up to two years earlier than current methods.

New clues to the origin and progression of multiple sclerosis

November 13, 2018
Mapping of a certain group of cells, known as oligodendrocytes, in the central nervous system of a mouse model of multiple sclerosis (MS), shows that they might have a significant role in the development of the disease. The ...

Mutations, CRISPR, and the biology behind movement disorders

November 12, 2018
Scientists at the RIKEN Center for Brain Science (CBS) in Japan have discovered how mutations related to a group of movement disorders produce their effects. Published in Proceedings of the National Academy of Sciences, the ...

In live brain function, researchers are finally seeing red

November 12, 2018
For years, green has been the most reliable hue for live brain imaging, but after using a new high-throughput screening method, researchers at the John B. Pierce Laboratory and the Yale School of Medicine, together with collaborators ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.