Researchers identify neuronal colonies responsible for ‘itchiness’ in the throats of mice.

Asthma, accompanied by lung inflammation, bronchoconstriction and airway hyper-responsiveness, is a significant public health burden.  Currently, asthma treatments such as anticholinergics target the hypersensitive nerves which connect the brain to parasympathetic neurons in the smooth muscle of the airway.  Therefore, insights into the neural mechanisms underlying the pathogenesis of asthma are highly desirable.  Now, a study from researchers at Johns Hopkins identifies skin itch receptors in the airways which appear to contribute to bronchoconstriction and airway hypersensitivity, which are hallmarks of asthma. The team state the biochemical receptor, known as a G protein-coupled receptor, was present on nerve cells in the lower respiratory tracts of lab mice.  The study is published in the journal Nature Neuroscience.

Earlier studies from the group involved patients who reported itchiness in their lungs just prior to full-blown asthma symptoms such as wheezing, which in turn inspired the researchers to study the sensation in the airway by asthma. Though the team had been studying the G protein-coupled receptor on the skin for many years, they had not yet looked for it in other parts of the body.  The current study uses fluorescent antibodies designed specifically to light up the receptor in mice, to identify G protein-coupled receptors on vagus nerves, which serve as a main biochemical connection between airway cells and the brain.

The current study explores the effects of the receptor on the airway using a protein called BAM8-22, which is an itch activator that specifically targets the G protein-coupled receptor, to induce a reaction. Results show 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 receptors are activated before an asthma-like attack.  To investigate what role vagus neurons have in this system the team repeated the experiments, while also activating the airway smooth muscles using acetylcholine, a neurotransmitter used throughout the nervous system to activate muscles. Data findings show that stimulation of the G protein-coupled receptor increased airway constriction more than activating the airway smooth muscles alone.

The group then infected specially bred mice carrying G protein-coupled receptors and those without the receptor with an influenza virus, which is known to trigger asthma attacks in humans. Results show that when the researchers 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.

The team surmise their data shows G protein-coupled receptors are expressed in a subset of vagal sensory neurons innervating the airway and mediates bronchoconstriction and airway hyper-responsiveness.  For the future, the researchers state that their experiments 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.

Source: Johns Hopkins


Researchers find 'itch receptors' in the throats of mice - neuroinnovations

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