The role of neuroeffector mechanisms in the pathogenesis of asthma.
Neural regulation of the airways consists of cholinergic excitatory, adrenergic inhibitory nerves and nonadrenergic, noncholinergic (NANC) nerves. NANC nerves can be either inhibitory or excitatory. Cholinergic nerves form the predominant bronchoconstrictor neural pathway in human airways. Acetylcholine controls neuronal and nonneuronal target cells via a short-lived action at nicotinic and muscarinic receptors. The most important control over acetylcholine release from postganglionic cholinergic nerves is exerted by acetylcholine itself. The M2 autoreceptor is located prejunctionally on postganglionic nerves. Its stimulation limits the further release of acetylcholine. A loss of function in the neuronal muscarinic M2 autoreceptor occurs after exposure to allergen, ozone, or viruses. In human airways, inhibitory NANC (i-NANC) mechanisms are the only neural bronchodilatory mechanisms. The presumed neurotransmitters of the i-NANC system are vasoactive intestinal peptide and nitric oxide. Substance P and neurokinin A have been implicated as the neurotransmitters mediating the excitatory part of the NANC nervous system. NK2 receptors are present on smooth muscle of both large and small airways and mediate part of the bronchoconstrictor effect of tachykinins. Most of the proinflammatory effects of substance P are mediated by the NK1 receptor. Tachykinin receptor antagonists are currently being developed as a possible anti-asthma treatment. An extensive cross-talk exists between nerves and the immune system. The complexity of the picture has increased further as it has become clear that classical neurotransmitters, such as acetylcholine and neuropeptides, are produced by nonneuronal cells.
Joos
G F
GF
Department of Respiratory Diseases 7K12E, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. guy.joos@rug.ac.be
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000502:physiology; D006801:Humans; D009451:Neuroeffector Junction / Q000502:physiology*