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Pathway Description
Methacholine M2 Bronchoconstriction Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-08-15
Last Updated: 2023-11-27
Methacholine is a parasympathomimetic bronchoconstrictor used to diagnose bronchial hyperreactivity in subjects who do not have clinically apparent asthma. It can be found under the brand name Provocholine. Asthma is a complex condition associated with phenomena such as airway hyperresponsiveness (AHR), in which the smooth muscle in the airways (ASM) excessively contracts in response to stimuli, reducing pulmonary function and causing symptoms such as difficulty breathing. Although the underlying pathology of AHR is complex, ASM contraction can be stimulated by cholinergic agonists that activate M3 muscarinic receptors that stimulate ASM contraction. Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction. In patients with AHR, a lower dose of methacholine is required to induce bronchoconstriction, which forms the basis for the methacholine challenge test to diagnose AHR. The inhibitory effect of M2 agonism by methacholine is likely also important, as shown by animal studies using mice with impaired M2 function, and by observations that eosinophilic inflammation, such as occurs in asthma, negatively impacts M2 function. Hence, asthmatic patients are more sensitive to inhaled cholinergic agonists such as methacholine; this forms the basis for the methacholine challenge test, which diagnoses AHR through an increased methacholine-induced response.
References
Methacholine M2 Bronchoconstriction Pathway References
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