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A new perspective on muscarinic receptor antagonism in obstructive airways diseases

Meurs, H., Oenema, T. A., Kistemaker, L. E. M. & Gosens, R., Jun-2013, In : Current Opinion in Pharmacology. 13, 3, p. 316-323 8 p.

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  • A new perspective on muscarinic receptor antagonism in obstructive airways diseases

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DOI

Acetylcholine has traditionally only been regarded as a neurotransmitter of the parasympathetic nervous system, causing bronchoconstriction and mucus secretion in asthma and COPD by muscarinic receptor activation on airway smooth muscle and mucus-producing cells. Recent studies in experimental models indicate that muscarinic receptor stimulation in the airways also induces pro-inflammatory, pro-proliferative and pro-fibrotic effects, which may involve activation of airway structural and inflammatory cells by neuronal as well as non-neuronal acetylcholine. In addition, mechanical changes caused by muscarinic agonist-induced bronchoconstriction may be involved in airway remodeling. Crosstalk between muscarinic receptors and beta(2)-adrenoceptors on airway smooth muscle causes a reduced bronchodilator response to beta(2)-agonists, and a similar mechanism could possibly apply to the poor inhibition of inflammatory and remodeling processes by these drugs. Collectively, these findings provide novel perspectives for muscarinic receptor antagonists in asthma and COPD, since these drugs may not only acutely affect cholinergic airways obstruction, but also have important beneficial effects on beta(2)-agonist responsiveness, airway inflammation and remodeling. The clinical relevance of these findings is presently under investigation and starting to emerge.

Original languageEnglish
Pages (from-to)316-323
Number of pages8
JournalCurrent Opinion in Pharmacology
Volume13
Issue number3
Publication statusPublished - Jun-2013

    Keywords

  • PROTEIN-KINASE-C, BRONCHIAL EPITHELIAL-CELLS, BETA-ADRENOCEPTOR FUNCTION, TRACHEAL SMOOTH-MUSCLE, HUMAN LUNG FIBROBLASTS, GUINEA-PIG MODEL, TIOTROPIUM BROMIDE, FUNCTIONAL ANTAGONISM, HOMOLOGOUS DESENSITIZATION, NEUTROPHILIC INFLAMMATION

ID: 5907468