Klein M K, Haberberger R V, Hartmann P, Faulhammer P, Lips K S, Krain B, Wess J, Kummer W, König P
Institut für Anatomie, Zentrum für Medizinische Struktur- und Zellbiologie, Lübeck, Germany.
Eur Respir J. 2009 May;33(5):1113-21. doi: 10.1183/09031936.00015108. Epub 2009 Feb 12.
Ciliary beating of airway epithelial cells drives the removal of mucus and particles from the airways. Mucociliary transport and possibly airway epithelial development are governed by muscarinic acetylcholine receptors but the precise roles of the subtypes involved are unknown. This issue was addressed by determining cilia-driven particle transport, ciliary beat frequency, and the composition and ultrastructural morphology of the tracheal epithelium in M1-M5 muscarinic receptor gene-deficient mice. Knockout of M3 muscarinic receptors prevented an increase in particle transport speed and ciliary beat frequency in response to muscarine. Furthermore, the ATP response after application of muscarine was blunted. Pretreatment with atropine before application of muscarine restored the response to ATP. Additional knockout of the M2 receptor in these mice partially restored the muscarine effect, most likely through the M1 receptor, and normalised the ATP response. M1, M4 and M5 receptor-deficient mice exhibited normal responses to muscarine. None of the investigated mutant mouse strains had any impairment of epithelial cellular structure or composition. In conclusion, M3 receptors stimulate whereas M2 receptors inhibit cilia-driven particle transport. The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptors are missing. None of the receptors is necessary for epithelial development.
气道上皮细胞的纤毛摆动推动气道内黏液和颗粒的清除。毒蕈碱型乙酰胆碱受体调控着黏液纤毛运输以及可能的气道上皮发育，但其中各亚型的确切作用尚不清楚。通过测定M1 - M5毒蕈碱受体基因缺陷小鼠中纤毛驱动的颗粒运输、纤毛摆动频率以及气管上皮的组成和超微结构形态，解决了这一问题。敲除M3毒蕈碱受体可阻止毒蕈碱引起的颗粒运输速度和纤毛摆动频率增加。此外，应用毒蕈碱后ATP反应减弱。在应用毒蕈碱前用阿托品预处理可恢复对ATP的反应。在这些小鼠中额外敲除M2受体可部分恢复毒蕈碱效应，最有可能是通过M1受体，并使ATP反应正常化。M1、M4和M5受体缺陷小鼠对毒蕈碱表现出正常反应。所研究的突变小鼠品系均未出现上皮细胞结构或组成的任何损伤。总之，M3受体刺激而M2受体抑制纤毛驱动的颗粒运输。如果缺失M3和M2受体，M1受体可增加纤毛驱动的颗粒运输。没有一种受体对于上皮发育是必需的。
