Schmidt Götz, Greif Isabelle, Müller Sabrina, Markmann Melanie, Edinger Fabian, Sander Michael, Koch Christian, Henrich Michael
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus Liebig University Giessen, Giessen, Germany.
Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine, Vidia St. Vincentius-Clinic Karlsruhe gAG, Karlsruhe, Germany.
Front Pharmacol. 2024 Sep 6;15:1401983. doi: 10.3389/fphar.2024.1401983. eCollection 2024.
The unique ability of the respiratory tract to protect the integrity of the airways by removing potentially harmful substances is defined as mucociliary clearance. This complex physiological mechanism protects the lower airways by ridding them of pollutants and pathogens. This study aimed to evaluate the potential influence of clinically relevant vasopressors on mucociliary clearance.
The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance under the influence of dopamine, norepinephrine, and vasopressin. Inhibitory substances were applied to elucidate relevant signal transduction cascades and the value and origin of calcium ions. Reverse-transcription polymerase chain reactions (RT-PCR) were performed to identify the expression of vasopressin receptor subtypes.
Dopamine, norepinephrine, and vasopressin significantly increased the PTV in a dose-dependent manner with half maximal effective concentrations of 0.58 µM, 1.21 µM, and 0.10 µM, respectively. Each substance increased the PTV via separate receptor pathways. While dopamine acted on D-like receptors to increase the PTV, norepinephrine acted on β-adrenergic receptors, and vasopressin acted on V receptors. RT-PCR revealed the expression of V in the murine whole trachea and tracheal epithelium. PTV increased when protein kinase A was inhibited and norepinephrine or vasopressin were applied, but not when dopamine was applied. Phospholipase C inhibition decreased the PTV when vasopressin was applied. In general, maximum PTV was significantly reduced when extracellular calcium entry was inhibited. When intracellular calcium stores were depleted, no increase in PTV was observed after administering all three substances. Inositol trisphosphate receptor activation was found to be pivotal in the increase in murine PTV after applying dopamine and vasopressin.
Dopamine, norepinephrine, and vasopressin accelerate the murine PTV via substance-specific receptor pathways. Further investigations should assess the value and interaction of these substances on mucociliary clearance in clinical practice.
呼吸道通过清除潜在有害物质来保护气道完整性的独特能力被定义为黏液纤毛清除功能。这种复杂的生理机制通过清除污染物和病原体来保护下呼吸道。本研究旨在评估临床相关血管加压素对黏液纤毛清除功能的潜在影响。
在多巴胺、去甲肾上腺素和血管加压素的影响下，测量分离的小鼠气管的颗粒运输速度（PTV），作为黏液纤毛清除功能的替代指标。应用抑制性物质以阐明相关信号转导级联以及钙离子的作用和来源。进行逆转录聚合酶链反应（RT-PCR）以鉴定血管加压素受体亚型的表达。
多巴胺、去甲肾上腺素和血管加压素均以剂量依赖性方式显著增加PTV，其半数最大有效浓度分别为0.58 μM、1.21 μM和0.10 μM。每种物质通过不同的受体途径增加PTV。多巴胺作用于D样受体以增加PTV，去甲肾上腺素作用于β肾上腺素能受体，而血管加压素作用于V受体。RT-PCR显示V在小鼠全气管和气管上皮中表达。当蛋白激酶A被抑制且应用去甲肾上腺素或血管加压素时，PTV增加，但应用多巴胺时则不然。应用血管加压素时，磷脂酶C抑制可降低PTV。一般来说，当细胞外钙内流被抑制时，最大PTV显著降低。当细胞内钙储备耗尽时，给予所有三种物质后均未观察到PTV增加。发现肌醇三磷酸受体激活在应用多巴胺和血管加压素后小鼠PTV增加中起关键作用。
多巴胺、去甲肾上腺素和血管加压素通过物质特异性受体途径加速小鼠PTV。进一步的研究应评估这些物质在临床实践中对黏液纤毛清除功能的作用和相互作用。
