Methacholine challenge test is used in bronchial hyperresponsiveness assessment. The mechanism by which methacholine induces bronchoconstriction is best described as:
- A Activation of M2 receptors on airway smooth muscle, releasing IP3 and causing calcium-mediated contraction
- B Blockade of β2 receptors on bronchial smooth muscle, reducing cAMP-mediated relaxation
- C Activation of M3 receptors on bronchial smooth muscle, stimulating Gq-PLC pathway with IP3-mediated intracellular calcium rise ✓
- D Direct stimulation of nicotinic receptors on bronchial smooth muscle
Correct answer: C. Activation of M3 receptors on bronchial smooth muscle, stimulating Gq-PLC pathway with IP3-mediated intracellular calcium rise
Explanation
Methacholine is a selective muscarinic agonist that is not metabolised by acetylcholinesterase and has preferential affinity for M3 receptors on airway smooth muscle. M3 receptor activation via Gq → PLC → IP3 → intracellular Ca2+ causes smooth muscle contraction and bronchoconstriction. M2 receptors on smooth muscle actually exert a countervailing inhibitory role. Methacholine has no significant β-receptor antagonism or nicotinic activity.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.