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Neural mechanisms in asthma

Authors


Professor Joos Ghent University Hospital, Department of Respiratory Diseases 7K12 1E, De Pintelaan 185, B-9000 Ghent, Belgium.

Abstract

Advances in the understanding of neural mechanisms in asthma may provide novel therapeutic approaches in the treatment of asthma. Excessive activity of cholinergic nerves may be important in asthma. Dysfunction of M2 muscarinic receptors in asthma may lead to excessive bronchoconstriction and mucus secretion and can be induced in animal models by a range of stimuli including allergen, viral infection, ozone, eosinophil products and cytokines. Cholinergic mechanisms may be especially important in certain types of patients and anticholinergic agents provide protection against bronchospasm due to psychogenic factors or beta2-blockers. Non-adrenergic non-cholinergic (NANC) mechanisms, both inhibitory (i-NANC) and excitatory (e-NANC), may play a significant role in the pathophysiology of asthma. The putative neurotransmitters, vasoactive interstinal polypeptide (VIP) and nitric oxide (NO), mediate neural bronchodilation in human airways. There does not appear to be a defect in the i-NANC system in moderate or severe asthma. e-NANC is mediated by the sensory neuropeptides substance P (SP) and the more potent bronchoconstrictor neurokinin A (NKA). Various studies suggest that the SP content of human airways is increased in asthma. Tachykinins are not only present in sensory nerves, but also are produced by inflammatory cells such as alveolar macrophages, dendritic cells, eosinophils, lymphocytes and neutrophils. They can be released into the airways by stimuli such as allergen and ozone. Evidence suggests that in addition to smooth muscle contraction, which is mediated mainly by NK2 receptors, tachykinins also cause mucus secretion, plasma extravasation and stimulate inflammatory and immune cells. These effects are mediated by NK1 receptors. Recent studies have shown that NK2 receptor antagonists such as saredutant partially inhibit NKA-induced bronchoconstriction in asthmatics. Thus, tachykinin receptor antagonists have potential as therapies for asthma.

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