Figure 2

Cholinergic receptors involved in neuronal acetylcholine release and function. Neuronal acetylcholine release is regulated by a network of afferent and efferent airway nerves that interact with their surrounding cells. Afferent C-fibers project to the subepithelial region where they can be activated by inflammatory mediators and non-specific stimuli. In asthma, epithelial damage can expose sensory nerve endings to the airway lumen, potentiating their activation. Activated C-fibers secrete neurokinins (NK) that exert local effects and facilitate ganglionic neurotransmission (peripheral reflex arc). In addition, the activated C-fiber increases the output of the vagal nerve through regulation in the central nervous system (CNS) (central reflex arc). Neurotransmission in parasympathetic ganglia of the airway is mediated by acetylcholine through nicotinic (N) and muscarinic M₁ receptors and can be markedly facilitated by inflammatory mediators (see text). Presynaptic muscarinic M₂ autoreceptors inhibit acetylcholine release and are dysfunctional in airway inflammation. The postganglionic neurons project primarily to mucus producing cells and airway smooth muscle, where neurotransmission is regulated by muscarinic M₁, M₂ and M₃ receptors, as indicated. As in the ganglia, prejunctional acetylcholine release is autoinhibited by muscarinic M₂ receptors that are dysfunctional in airway inflammation. Acetylcholine release is augmented further by direct effects of inflammatory mediators on facilitatory presynaptic receptors. See the text for further detail.