Cysteinyl-leukotrienes and β2-adrenoceptor Function in Asthma
Author Information
Author(s): Rovati G Enrico, Baroffio Michele, Citro Simona, Brichetto Lorenzo, Ravasi Saula, Milanese Manlio, Crimi Emanuele, Brusasco Vito
Primary Institution: University of Milan, Italy; University of Genoa, Italy
Hypothesis
Leukotriene D4 (LTD4) and allergen challenge cause β2-adrenoceptor desensitization through the activation of protein kinase C (PKC).
Conclusion
LTD4 induces β2-adrenoceptor desensitization in human airway smooth muscle cells, mediated through PKC activation.
Supporting Evidence
- LTD4 and PMA caused significant reductions in cAMP accumulation in human airway smooth muscle cells.
- Montelukast and GF109203X prevented the desensitization effects of LTD4.
- Allergen challenge shifted the concentration-response curves to salbutamol in bronchial rings.
Takeaway
In asthma, a substance called LTD4 makes it harder for a medicine to work that usually helps open up the airways. But using a specific blocker can help the medicine work better.
Methodology
The study evaluated cAMP accumulation in human airway smooth muscle cells and bronchial rings after exposure to LTD4 and allergen, using various inhibitors.
Participant Demographics
Bronchial rings obtained from 6 non-asthmatic patients undergoing thoracotomy for lung cancer.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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