ArticleRespiratory research2006
Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse.
Article in Respiratory research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 75 citations in OpenAlex.
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Modeling Intestinal Stem Cell Function with Organoids.International journal of molecular sciences · 2021Review
- 5-HTJournal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2021Article
- Organic Cation Transporters in the Lung-Current and Emerging (Patho)Physiological and Pharmacological Concepts.International journal of molecular sciences · 2020Review
- Acetylcholine From Tuft Cells: The Updated Insights Beyond Its Immune and Chemosensory Functions.Frontiers in cell and developmental biology · 2020Review
- Acetylcholine signaling system in progression of lung cancers.Pharmacology & therapeutics · 2019Review
- Caveolin-3 differentially orchestrates cholinergic and serotonergic constriction of murine airways.Scientific reports · 2018Article
- Beclomethasone dipropionate and formoterol fumarate synergistically interact in hyperresponsive medium bronchi and small airways.Respiratory research · 2018Article
- Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment.Current neuropharmacology · 2017Review
- Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced Smooth Muscle Constriction in Murine Airways.Frontiers in physiology · 2017Article
- Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.Frontiers in pharmacology · 2016Article
- Cholinergic activity as a new target in diseases of the heart.Molecular medicine (Cambridge, Mass.) · 2015Review
- Non-neuronal cholinergic system in airways and lung cancer susceptibility.Translational lung cancer research · 2013Review
- Article
- Alterations in the non-neuronal acetylcholine synthesis and release machinery in esophageal epithelium.Life sciences · 2012Article
- Luminal cholinergic signalling in airway lining fluid: a novel mechanism for activating chloride secretion via Ca²⁺-dependent Cl⁻ and K⁺ channels.British journal of pharmacology · 2012Article
- Local small airway epithelial injury induces global smooth muscle contraction and airway constriction.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Article
- Cholinergic regulation of airway inflammation and remodelling.Journal of allergy · 2012Article
- Muscarinic receptor antagonists: effects on pulmonary function.Handbook of experimental pharmacology · 2012Review
- Ion transport by pulmonary epithelia.Journal of biomedicine & biotechnology · 2011Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundIt has been proposed that serotonin (5-HT)-mediated constriction of the murine trachea is largely dependent on acetylcholine (ACh) released from the epithelium. We recently demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs), which are also expressed by airway epithelial cells. Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs.
methodsWe tested this hypothesis by analysing bronchoconstriction in precision-cut murine lung slices using OCT and muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was measured by HPLC, and the tissue distribution of OCT isoforms was determined by immunohistochemistry.
resultsEpithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 +/- 10 % of the content of the epithelium-denuded trachea, n = 9) than in wild-type mice (16.8 +/- 3.6 %, n = 11). In wild-type mice, 5-HT (1 microM) caused a bronchoconstriction that slightly exceeded that evoked by muscarine (1 microM) in intact bronchi but amounted to only 66% of the response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction was undiminished in M2/M3 muscarinic ACh receptor double-knockout mice which were entirely unresponsive to muscarine. Corticosterone (1 microM) significantly reduced 5-HT-induced bronchoconstriction in wild-type and OCT1/2 double-knockout mice, but not in OCT3 knockout mice. This effect persisted after removal of the bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth muscle.
conclusionThe doubling of airway epithelial ACh content in OCT1/2-/- mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from the respiratory epithelium. This effect, however, does not contribute to 5-HT-induced constriction of murine intrapulmonary bronchi. Instead, this activity involves 1) a non-cholinergic epithelium-dependent component, and 2) direct stimulation of bronchial smooth muscle cells, a response which is partly sensitive to acutely administered corticosterone acting on OCT3. These data provide new insights into the mechanisms involved in 5-HT-induced bronchoconstriction, including novel information about non-genomic, acute effects of corticosteroids on bronchoconstriction.
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