MUSCARINIC RECEPTOR SUBTYPES IN AIRWAYS

Muscarinic receptor subtypes in the airways appear to subserve different physiological functions. M1-receptors facilitate neurotransmission through parasympathetic ganglia and enhance cholinergic reflexes, but are also localized to alveolar walls. M2-receptors act as autoreceptors on post-ganglionic cholinergic nerves and inhibit acetylcholine release. There is some evidence that they may be defective in asthma (as a consequence of airway inflammation?) and this may enhance cholinergic reflexes and account for beta-blocker-induced asthma. M2-receptors in airway smooth muscle may also counteract the bronchodilator action of beta-agonists. M3-receptors mediate contractile responses in airway smooth muscle via phosphoinositide hydrolysis, and are the predominant receptors on submucosal glands and airway vascular endothelium. M4- and M5-receptors have not been identified in human airways, but in rabbit lung M4-receptors are expressed on alveolar walls and smooth muscle. Anticholinergic drugs which selectively block M3 and M1-receptors may have an advantage over currently used non-selective antagonists in the treatment of airway obstruction.