Evidence map›Paper›PMID 40940383›Full record

ArticleScientific reports2025

Amitriptyline inhibits bronchoconstriction independent of direct receptor binding and reduces number of caveolae.

Virag Klein, Anna Michely, Paulina Hempel, Istvan Katona, Klaus Tenbrock, Christian Martin, Eva Verjans

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Virag Klein *Department of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany.
Anna Michely *Department of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany.
Paulina HempelDepartment of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany.
Istvan KatonaInstitute of Neuropathology, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany.
Klaus TenbrockDepartment of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany.
Christian MartinInstitute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany.
Eva VerjansDepartment of Pediatrics, Medical Faculty, RWTH Aachen, University Hospital Aachen, Aachen, Germany. everjans@ukaachen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bronchial asthma is a chronic inflammatory disease with rising prevalence worldwide. Apart from the immunological role of the tricyclic antidepressant amitriptyline in bronchial asthma, there is emerging evidence that inhaled amitriptyline directly reduces acute bronchoconstriction. However, the mechanism by which amitriptyline influences bronchial tone remains poorly understood. To influence bronchoconstriction, rat precision-cut lung slices treated with varying concentrations of amitriptyline (0-5 µM) and incubated with inhibitors targeting different signaling pathways. Amitriptyline reduces acetylcholine- and serotonin-induced bronchoconstriction. Neither the muscarinic antagonist ipratropium nor the phospholipase C inhibitor U73122, nor the protein kinase C inhibitor chelerythrine diminished the effect of amitriptyline. Inhibition of calcium sensitizing and induction failed to alter amitriptyline's effect on bronchoconstriction. Caveolae-as part of the plasma membrane-display a microenvironment, where regulation of signal transduction takes place. Similar to methyl ß cyclodextrin (MBCD), a common substance to destroy caveolae, amitriptyline dramatically reduced the number of caveolae in lung tissue. However, unlike MBCD, this effect could not be explained by cholesterol depletion alone, as cholesterol repletion did not reverse amitriptyline's effect. Furthermore, neither simvastatin (a lipid lowering agent) nor cytochalasin D (an inhibitor of actin polymerization), influenced the inhibitory effect of amitriptyline on bronchoconstriction. In conclusion, amitriptyline inhibits bronchoconstriction independently of direct receptor binding or interaction. It also reduces the total number of caveolae without effects on cholesterol lowering pathways or actin depolymerization. A more general mechanism seems likely, as inhibition of single signal transduction pathways failed. Further studies are required to elucidate the underlying mechanisms.

Indexed as

AmitriptylineBronchoconstrictionCaveolaeAnimalsbeta-CyclodextrinsLungMaleRatsSignal TransductionAmitriptylinebeta-CyclodextrinsAmitriptylineBronchial asthmaBronchoconstrictionLipid raftsMechanism

Identifiers

PMID40940383
PMCPMC12432258

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.