{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:16:12Z","timestamp":1753892172806,"version":"3.41.2"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dopamine, norepinephrine, and vasopressin significantly increased the PTV in a dose-dependent manner with half maximal effective concentrations of 0.58\u00a0\u00b5M, 1.21\u00a0\u00b5M, and 0.10\u00a0\u00b5M, respectively. Each substance increased the PTV via separate receptor pathways. While dopamine acted on D<jats:sub>1<\/jats:sub>-like receptors to increase the PTV, norepinephrine acted on \u03b2-adrenergic receptors, and vasopressin acted on V<jats:sub>1a<\/jats:sub> receptors. RT-PCR revealed the expression of V<jats:sub>1a<\/jats:sub> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1401983","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:38:49Z","timestamp":1725597529000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dopamine, norepinephrine, and vasopressin accelerate particle transport velocity in murine tracheal epithelium via substance-specific receptor pathways: dependency on intra- and extracellular Ca2+ sources"],"prefix":"10.3389","volume":"15","author":[{"given":"G\u00f6tz","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Greif","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Markmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Edinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Sander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"652158","DOI":"10.3389\/fcvm.2021.652158","article-title":"Mucociliary clearance scans show infants undergoing congenital cardiac surgery have poor airway clearance function","volume":"8","author":"Adams","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13613-022-01021-9","article-title":"Timing of vasoactive agents and corticosteroid initiation in septic shock","volume":"12","author":"Ammar","year":"2022","journal-title":"Ann. Intensive Care"},{"key":"B3","doi-asserted-by":"publisher","first-page":"481","DOI":"10.4097\/KJA.22805","article-title":"Postoperative norepinephrine versus dopamine in patients undergoing noncardiac surgery: a propensity-matched analysis using a nationwide intensive care database","volume":"76","author":"Aoki","year":"2023","journal-title":"Korean J. Anesthesiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0129305","DOI":"10.1371\/journal.pone.0129305","article-title":"Vasopressors for the treatment of septic shock: systematic review and meta-analysis","volume":"10","author":"Avni","year":"2015","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1097\/01.CCM.0000299741.32078.E9","article-title":"Following tracheal intubation, mucus flow is reversed in the semirecumbent position: possible role in the pathogenesis of ventilator-associated pneumonia","volume":"36","author":"Bassi","year":"2008","journal-title":"Crit. Care Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1161\/CIRCRESAHA.120.318234","article-title":"CAMP imaging at ryanodine receptors reveals \u03b22-adrenoceptor driven arrhythmias","volume":"129","author":"Berisha","year":"2021","journal-title":"Circulation Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1038\/sj.bjp.0706103","article-title":"Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line, 16HBE14o-","volume":"144","author":"Bernard","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"B8","first-page":"273","article-title":"Regulation of inositol 1,4,5-trisphosphate receptors by phosphorylation and adenine nucleotides","volume-title":"Current topics in membranes","author":"Betzenhauser","year":"2010"},{"key":"B9","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S1043-2760(00)00304-0","article-title":"Vasopressin receptors","volume":"11","author":"Birnbaumer","year":"2000","journal-title":"Trends Endocrinol. Metabolism"},{"key":"B10","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3389\/fncel.2013.00157","article-title":"The role of dopamine signaling in epileptogenesis","volume":"7","author":"Bozzi","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1378\/chest.89.3.410","article-title":"Oxidant-mediated ciliary dysfunction. Possible role in airway disease","volume":"89","author":"Burman","year":"1986","journal-title":"Chest"},{"key":"B12","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.str.2023.04.009","article-title":"Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives","volume":"31","author":"Cholak","year":"2023","journal-title":"Structure"},{"key":"B13","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1165\/rcmb.2005-0417OC","article-title":"Ciliary beat frequency is maintained at a maximal rate in the small airways of mouse lung slices","volume":"35","author":"Delmotte","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1186\/s12871-023-02343-2","article-title":"Pressure-controlled ventilation-volume guaranteed mode improves bronchial mucus transport velocity in patients during laparoscopic surgery for gynecological oncology: a randomized controlled study","volume":"23","author":"Deng","year":"2023","journal-title":"BMC Anesthesiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.bja.2023.08.022","article-title":"Vasopressors to treat postoperative hypotension after adult noncardiac, non-obstetric surgery: a systematic review","volume":"131","author":"Douglas","year":"2023","journal-title":"Br. J. Anaesth."},{"key":"B16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1097\/00000542-197901000-00006","article-title":"Mucociliary clearance in the canine lung during and after general anesthesia","volume":"50","author":"Forbes","year":"1979","journal-title":"Anesthesiology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1152\/japplphysiol.00755.2001","article-title":"Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells","volume":"92","author":"Frohock","year":"2002","journal-title":"J. Appl. Physiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1111\/j.1472-8206.2008.00633.x","article-title":"The Hill equation: a review of its capabilities in pharmacological modelling","volume":"22","author":"Goutelle","year":"2008","journal-title":"Fundam. Clin. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.3390\/molecules26206097","article-title":"Nicotinic acetylcholine receptors in the respiratory tract","volume":"26","author":"Hollenhorst","year":"2021","journal-title":"Molecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jointm.2022.05.001","article-title":"Alternatives to norepinephrine in septic shock: which agents and when?","volume":"2","author":"Jozwiak","year":"2022","journal-title":"J. Intensive Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1186\/s12931-020-01555-1","article-title":"Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium","volume":"21","author":"Kamiya","year":"2020","journal-title":"Respir. Res."},{"key":"B22","first-page":"107","article-title":"Volatile anesthetics and mucociliary clearance","volume":"74","author":"Kesimci","year":"2008","journal-title":"Minerva Anestesiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00134-004-2235-3","article-title":"Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity","volume":"30","author":"Kilgour","year":"2004","journal-title":"Intensive Care Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"21009","DOI":"10.1038\/s41598-023-48178-2","article-title":"Norepinephrine prevents hypotension in older patients under spinal anesthesia with intravenous propofol sedation: a randomized controlled trial","volume":"13","author":"Kim","year":"2023","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ceca.2014.02.001","article-title":"Ca\u00b2\u207a signaling and fluid secretion by secretory cells of the airway epithelium","volume":"55","author":"Lee","year":"2014","journal-title":"Cell Calcium"},{"key":"B26","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.semcdb.2020.11.007","article-title":"Motile cilia and airway disease","volume":"110","author":"Legendre","year":"2021","journal-title":"Seminars Cell Dev. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1111\/ejn.16205","article-title":"Dopamine and noradrenaline activate spinal astrocyte endfeet via D1-like receptors","volume":"59","author":"Montalant","year":"2023","journal-title":"Eur. J. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0066921","DOI":"10.1128\/AAC.00669-21","article-title":"Echinocandins accelerate particle transport velocity in the murine tracheal epithelium: dependency on intracellular Ca2+ stores","volume":"65","author":"M\u00fcller","year":"2021","journal-title":"Antimicrob. agents Chemother."},{"key":"B29","doi-asserted-by":"publisher","first-page":"6735","DOI":"10.1016\/s0021-9258(17)37437-9","article-title":"Cyclic AMP-dependent phosphorylation of an immunoaffinity-purified homotetrameric inositol 1,4,5-trisphosphate receptor (type I) increases Ca2+ flux in reconstituted lipid vesicles","volume":"269","author":"Nakade","year":"1994","journal-title":"J. Biol. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2772","DOI":"10.1378\/chest.128.4.2772","article-title":"Mucociliary clearance is impaired in acutely ill patients","volume":"128","author":"Nakagawa","year":"2005","journal-title":"Chest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1002\/cphy.c170031","article-title":"Store-operated calcium entry mediated by ORAI and STIM","volume":"8","author":"Nguyen","year":"2018","journal-title":"Compr. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4289","DOI":"10.26355\/eurrev_202206_29067","article-title":"Effects of sugammadex and neostigmine on mucociliary clearance in general anesthesia","volume":"26","author":"Ozciftci","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.immuni.2020.03.005","article-title":"Chemosensory cell-derived acetylcholine drives tracheal mucociliary clearance in response to virulence-associated formyl peptides","volume":"52","author":"Perniss","year":"2020","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","first-page":"38","DOI":"10.14797\/mdcvj.1245","article-title":"Vasoplegia: a review","volume":"19","author":"Ratnani","year":"2023","journal-title":"Methodist DeBakey Cardiovasc. J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3974","DOI":"10.1111\/jcmm.17990","article-title":"Cilia-related diseases","volume":"27","author":"Ren","year":"2023","journal-title":"J. Cell Mol. Med."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121430-20211009-01442","article-title":"Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021, interpretation and expectation","author":"Ruiqiang","year":"2021","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B37","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1146\/annurev.physiol.69.040705.141253","article-title":"Regulation of mammalian ciliary beating","volume":"69","author":"Salathe","year":"2007","journal-title":"Annu. Rev. Physiology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"7302","DOI":"10.1073\/pnas.83.19.7302","article-title":"Mechanosensitivity of cultured ciliated cells from the mammalian respiratory tract: implications for the regulation of mucociliary transport","volume":"83","author":"Sanderson","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1097\/SHK.0000000000000325","article-title":"Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock","volume":"43","author":"Sarkar","year":"2015","journal-title":"Shock"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1155930","DOI":"10.3389\/fphar.2023.1155930","article-title":"A 20:1 synergetic mixture of cafedrine\/theodrenaline accelerates particle transport velocity in murine tracheal epithelium via IP3 receptor-associated calcium release","volume":"14","author":"Schmidt","year":"","journal-title":"Front. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"16216","DOI":"10.1038\/s41598-023-43342-0","article-title":"A fixed 20:1 combination of cafedrine\/theodrenaline increases cytosolic Ca2+ concentration in human tracheal epithelial cells via ryanodine receptor-mediated Ca2+ release","volume":"13","author":"Schmidt","year":"","journal-title":"Sci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"C402","DOI":"10.1152\/ajpcell.00355.2015","article-title":"Orai channel-mediated Ca2+ signals in vascular and airway smooth muscle","volume":"310","author":"Spinelli","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1113\/jphysiol.2004.068171","article-title":"Regulation of human airway ciliary beat frequency by intracellular pH","volume":"560","author":"Sutto","year":"2004","journal-title":"J. Physiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13054-022-03960-y","article-title":"Dopamine use and its consequences in the intensive care unit: a cohort study utilizing the Japanese Intensive care PAtient Database","volume":"26","author":"Suzuki","year":"2022","journal-title":"Crit. Care"},{"key":"B45","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0143-4179(98)90049-X","article-title":"Characterization of vasopressin receptor in rat lung","volume":"32","author":"Tahara","year":"1998","journal-title":"Neuropeptides"},{"key":"B46","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1165\/ajrcmb.19.2.3134","article-title":"Vasopressin stimulates ciliary motility of rabbit tracheal epithelium: role of V1b receptor-mediated Ca2+ mobilization","volume":"19","author":"Tamaoki","year":"1998","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.ceca.2016.10.005","article-title":"Regulation of IP3 receptors by cyclic AMP","volume":"63","author":"Taylor","year":"2017","journal-title":"Cell Calcium"},{"key":"B48","doi-asserted-by":"publisher","first-page":"12979","DOI":"10.1074\/jbc.M109.096016","article-title":"Regulation of inositol 1,4,5-trisphosphate receptors by cAMP independent of cAMP-dependent protein kinase","volume":"285","author":"Tovey","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1083\/jcb.200803172","article-title":"Selective coupling of type 6 adenylyl cyclase with type 2 IP3 receptors mediates direct sensitization of IP3 receptors by cAMP","volume":"183","author":"Tovey","year":"2008","journal-title":"J. Cell Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12576-023-00878-0","article-title":"Physiological functions of calcium signaling via Orai1 in cancer","volume":"73","author":"Umemura","year":"2023","journal-title":"J. Physiol. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e0143163","DOI":"10.1371\/journal.pone.0143163","article-title":"Galactomannan and zymosan block the epinephrine-induced particle transport in tracheal epithelium","volume":"10","author":"Weiterer","year":"2015","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e91705","DOI":"10.1371\/journal.pone.0091705","article-title":"Tumor necrosis factor alpha induces a serotonin dependent early increase in ciliary beat frequency and epithelial transport velocity in murine tracheae","volume":"9","author":"Weiterer","year":"2014","journal-title":"PLoS One"},{"key":"B53","doi-asserted-by":"publisher","first-page":"S143","DOI":"10.1513\/AnnalsATS.201802-128AW","article-title":"Airway epithelial differentiation and mucociliary clearance","volume":"15","author":"Whitsett","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B54","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3390\/cells4030315","article-title":"Cyclic GMP and cilia motility","volume":"4","author":"Wyatt","year":"2015","journal-title":"Cells"},{"key":"B55","doi-asserted-by":"publisher","first-page":"18028","DOI":"10.1073\/pnas.0906560106","article-title":"Beta-adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel","volume":"106","author":"Zhou","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1401983\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T04:38:53Z","timestamp":1725597533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1401983\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":55,"alternative-id":["10.3389\/fphar.2024.1401983"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1401983","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"article-number":"1401983"}}