ArticleBritish journal of pharmacology2012
Non-bronchodilating mechanisms of tiotropium prevent airway hyperreactivity in a guinea-pig model of allergic asthma.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- The Impact of Muscarinic Receptor Antagonists on Airway Inflammation: A Systematic Review.International journal of chronic obstructive pulmonary diseasePooled it
- V0162 a new long-acting bronchodilator for treatment of chronic obstructive lung diseases: preclinical and clinical results.Respiratory research · 2015Trial
- Role of animal models in biomedical research: a review.Laboratory animal research · 2022Review
- Muscarinic receptor antagonists and airway inflammation: A systematic review on pharmacological models.Heliyon · 2022Review
- Can GPCRs Be Targeted to Control Inflammation in Asthma?Advances in experimental medicine and biology · 2021Article
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
- Noninvasive allergic sinus congestion and resolution assessments using microcomputed tomography imaging.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- Animal models of asthma: utility and limitations.Journal of asthma and allergy · 2017Review
- The evidence on tiotropium bromide in asthma: from the rationale to the bedside.Multidisciplinary respiratory medicine · 2017Review
- Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced Smooth Muscle Constriction in Murine Airways.Frontiers in physiology · 2017Article
- Tiotropium in asthma: back to the future of anticholinergic treatment.Clinical and molecular allergy : CMA · 2017Review
- Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke-Exposed Mice.The Journal of pharmacology and experimental therapeutics · 2016Article
- Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.Therapeutic advances in chronic disease · 2014Review
- The role of tiotropium in the management of asthma.Asia Pacific allergy · 2012Article
- Adjustment of sensitisation and challenge protocols restores functional and inflammatory responses to ovalbumin in guinea-pigs.Journal of pharmacological and toxicological methodsArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeAsthma is characterized by reversible bronchoconstriction and airway hyperreactivity. Although M(3) muscarinic receptors mediate bronchoconstriction, non-selective muscarinic receptor antagonists are not currently recommended for chronic control of asthma. We tested whether selective blockade of M(3) receptors, at the time of antigen challenge, blocks subsequent development of airway hyperreactivity in antigen-challenged guinea-pigs. EXPERIMENTAL APPROACH: Ovalbumin-sensitized guinea-pigs were pretreated with 1 µg·kg(-1) of a kinetically selective M(3) receptor antagonist, tiotropium, or 1 mg·kg(-1) of a non-selective muscarinic receptor antagonist, atropine, and challenged with inhaled ovalbumin. Animals were anaesthetized, paralyzed, ventilated and vagotomized 24 h later. We measured vagally mediated bronchoconstriction and i.v. ACh-induced bronchoconstriction. KEY
resultsElectrical stimulation of both vagus nerves induced frequency-dependent bronchoconstriction in sensitized animals that was significantly increased after antigen challenge. Antigen-induced hyperreactivity was completely blocked by tiotropium pretreatment but only partially blocked by atropine pretreatment. Surprisingly, although tiotropium blocked bronchoconstriction induced by i.v. ACh, it did not inhibit vagally-induced bronchoconstriction in sensitized controls, suggesting that tiotropium does not block hyperreactivity by blocking receptors for vagally released ACh. Rather, tiotropium may have worked through an anti-inflammatory mechanism, since it inhibited eosinophil accumulation in the lungs and around nerves. CONCLUSIONS AND IMPLICATIONS: These data confirm that testing M(3) receptor blockade with exogenous ACh does not predict vagal blockade. Our data also suggest that selective blockade of M(3) receptors may be effective in asthma via mechanisms that are separate from inhibition of bronchoconstriction.
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Registered trials
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 OpenQuestion graph.