Increased release of acetylcholine from the parasympathetic nerves may contribute to the hyperresponsiveness characteristic of asthma. Feedback of acetylcholine onto inhibitory M2 muscarinic receptors on the parasympathetic nerves decreases the further release of acetylcholine. Dysfunctions of these neuronal M2 receptors increases the release of acetylcholine and leads to hyperresponsiveness in animals. In antigen-challenged guinea pigs, hyperresponsiveness is entirely mediated by loss of M2 muscarinic receptor function. Loss of M2 receptor function is also associated with hyperresponsiveness in humans with asthma when they are exposed to ozone or have a naturally acquired viral infection. There are several different mechanisms for loss of M2 muscarinic receptor function, including blockade of the receptor by eosinophil major basic protein, decreased affinity of the receptor for agonists, and decreased M2-receptor gene expression. The different mechanisms are described and discussed in the context of asthma and of the various animal models of hyperresponsiveness.
ASJC Scopus subject areas
- Immunology and Allergy