Muscarinic receptor subtypes: Implications for lung disease

Abstract

Several subtypes of muscarinic receptor have now been identified and have been found recently in the airways of several species, including man, a discovery that may have important clinical implications. M1 receptors may be found in parasympathetic ganglia, M2 receptors on cholinergic nerves (autoreceptors), and M3 receptors on airway smooth muscle and mucus secreting glands. It is suggested that a defect in M2 receptor function may help to explain why asthma may be induced by beta blocking drugs. Further elucidation of the physiological role for these receptor subtypes will probably depend on the development of more selective antagonists. Drugs such as methoctramine, which have a high degree of selectivity for M2 receptors, are promising tools for elucidating the role of muscarinic receptor subtypes, but drugs with a higher selectivity for M1 and M3 receptors are likely to be most useful clinically in airway disease; in particular, M3 blockers will not be associated with increased acetylcholine release. The recent availability of clones muscarinic receptor subtypes, and the application of in situ hybridisation techniques, should also point the way to studying differential regulation of muscarinic receptor expression in disease.