Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands.
Curr Opin Pharmacol. 2013 Jun;13(3):316-23. doi: 10.1016/j.coph.2013.04.004. Epub 2013 May 3.
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 β2-adrenoceptors on airway smooth muscle causes a reduced bronchodilator response to β2-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 β2-agonist responsiveness, airway inflammation and remodeling. The clinical relevance of these findings is presently under investigation and starting to emerge.
乙酰胆碱传统上仅被认为是副交感神经系统的神经递质，通过气道平滑肌和黏液细胞上的毒蕈碱受体激活，导致哮喘和 COPD 中的支气管收缩和黏液分泌。最近在实验模型中的研究表明，气道中的毒蕈碱受体刺激也会引起促炎、促增殖和促纤维化作用，这可能涉及到神经元和非神经元乙酰胆碱激活气道结构细胞和炎症细胞。此外，毒蕈碱激动剂诱导的支气管收缩引起的机械变化可能与气道重塑有关。气道平滑肌上的毒蕈碱受体和β2-肾上腺素能受体之间的串扰导致对β2-激动剂的支气管扩张反应减弱，类似的机制可能适用于这些药物对炎症和重塑过程抑制作用不佳的情况。总的来说，这些发现为哮喘和 COPD 中的毒蕈碱受体拮抗剂提供了新的视角，因为这些药物不仅可以急性影响胆碱能气道阻塞，而且对β2-激动剂的反应性、气道炎症和重塑具有重要的有益作用。这些发现的临床相关性目前正在研究中，并开始显现。
