ArticleBritish journal of pharmacology2009
Molecular mechanisms for the persistent bronchodilatory effect of the beta 2-adrenoceptor agonist salmeterol.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
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- Leveraging Machine Learning-Guided Molecular Simulations Coupled with Experimental Data to Decipher Membrane Binding Mechanisms of Aminosterols.Journal of chemical theory and computation · 2024Article
- Kinetic analysis of endogenous βBritish journal of pharmacology · 2023Article
- An evolving perspective on novel modified release drug delivery systems for inhalational therapy.Expert opinion on drug delivery · 2023Review
- Interaction With the Lipid Membrane Influences Fentanyl Pharmacology.Advances in drug and alcohol research · 2022Article
- Membrane-Facilitated Receptor Access and Binding Mechanisms of Long-ActingMolecular pharmacology · 2021Article
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
- Does the Lipid Bilayer Orchestrate Access and Binding of Ligands to Transmembrane Orthosteric/Allosteric Sites of G Protein-Coupled Receptors?Molecular pharmacology · 2019Review
- Link between a highMedChemComm · 2018Review
- Cell membranes… and how long drugs may exert beneficial pharmacological activity in vivo.British journal of clinical pharmacology · 2016Review
- Effects of target binding kinetics on in vivo drug efficacy: koff , kon and rebinding.British journal of pharmacology · 2016Article
- Salmeterol Efficacy and Bias in the Activation and Kinase-Mediated Desensitization of β2-Adrenergic Receptors.Molecular pharmacology · 2015Article
- 'Partial' competition of heterobivalent ligand binding may be mistaken for allosteric interactions: a comparison of different target interaction models.British journal of pharmacology · 2015Article
- Simplified models for heterobivalent ligand binding: when are they applicable and which are the factors that affect their target residence time.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.Respiratory research · 2013Article
- Exploring avidity: understanding the potential gains in functional affinity and target residence time of bivalent and heterobivalent ligands.British journal of pharmacology · 2013Review
- Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism.Naunyn-Schmiedeberg's archives of pharmacology · 2012Review
- Slow receptor dissociation is not a key factor in the duration of action of inhaled long-acting β2-adrenoceptor agonists.British journal of pharmacology · 2012Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundBeta(2)-adrenoceptor agonists are effective bronchodilators. In vitro studies demonstrated long-lasting airway smooth muscle relaxation by salmeterol after washout, the quick disappearance of this effect in presence of antagonists and its recovery after antagonist removal. Current explanations invoke salmeterol accumulation in the membrane ('diffusion microkinetic' model) or the existence of salmeterol-binding 'exosites'. An alternative model based on 'rebinding' of a dissociated ligand to the receptor molecules also produces an apparent decrease in the ligand's dissociation rate in the absence of competing ligands. PURPOSE AND APPROACH: Computer-assisted simulations were performed to follow the receptor-occupation by a salmeterol-like ligand and a competing ligand as a function of time. The aptness of the models to describe the above in vitro findings was evaluated. KEY
resultsThe 'diffusion microkinetic' model is sufficient to explain a long-lasting beta(2)-adrenoceptor stimulation and reassertion as long as the membrane harbors a high concentration of the agonist. At lower concentration, 'rebinding' and, in second place, 'exosite' binding are likely to become operational. CONCLUSIONS AND IMPLICATIONS: The 'rebinding' and 'exosite' binding mechanisms take place at a sub-cellular/molecular scale. Pending their demonstration by experiments on appropriate, simple models such as intact cells or membranes thereof, these mechanisms remain hypothetical in the case of salmeterol. Airway smooth muscle contraction could also be governed by additional mechanisms that are particular to this macroscopic approach.
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