Related Experiment Videos
Interactions of glucocorticoids and beta 2-agonists
I M Adcock1, D A Stevens, P J Barnes
1Dept of Thoracic Medicine, Imperial College of Science, Technology & Medicine, London, UK.
The European Respiratory Journal
|January 1, 1996
Summary
High-dose beta 2-agonists may reduce glucocorticoid receptor (GR) DNA binding in lung cells, potentially causing functional antiglucocorticoid activity. This interaction might explain increased asthma morbidity linked to rising beta 2-agonist use.
Area of Science:
- Pharmacology
- Molecular Biology
- Respiratory Medicine
Background:
- Beta 2-adrenoreceptor agonists and glucocorticosteroids are primary asthma treatments, often co-administered.
- Glucocorticoids exert anti-inflammatory effects via activated glucocorticoid receptors (GRs).
- GRs interact with transcription factors like AP-1 and NF-kappa B to regulate inflammatory gene synthesis.
Purpose of the Study:
- To investigate the interaction between beta 2-agonists and GRs in lung cells.
- To explore the role of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in this interaction.
- To determine if high-dose beta 2-agonists can exhibit antiglucocorticoid activity.
Main Methods:
- The study focuses on molecular interactions within lung cells.
- It examines the effects of beta 2-agonists on GR DNA-binding.
- Investigates the role of CREB activation in modulating GR function.
Main Results:
- High doses of beta 2-agonists activate CREB in lung cells.
- Activated CREB inhibits the ability of GR to bind DNA.
- This inhibition suggests a potential for functional antiglucocorticoid activity.
Conclusions:
- High-dose beta 2-agonists may possess antiglucocorticoid properties by interfering with GR DNA binding.
- This mechanism could contribute to the observed increase in asthma morbidity and mortality in regions with high beta 2-agonist consumption.
- Further research is warranted to elucidate the clinical implications of this drug interaction.