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Bronchial hyperresponsiveness: insights into new signaling molecules
Yassine Amrani1, Omar Tliba, Deepak A Deshpande
1Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Medical Center, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. amrani@mail.med.upenn.edu
Current Opinion in Pharmacology
|May 14, 2004
Summary
Cyclic ADP-ribose (cADPr) influences calcium signaling in airway smooth muscle cells, contributing to asthma-related hyperresponsiveness. Understanding these pathways may reveal new therapeutic targets for airway diseases.
Area of Science:
- Cellular signaling pathways
- Respiratory system physiology
- Pharmacology of airway diseases
Background:
- Signaling molecules are crucial in airway disease pathophysiology.
- Cyclic ADP-ribose (cADPr) activates ryanodine receptors and modulates calcium responses in airway smooth muscle (ASM) cells.
- Cytokine-induced "non-specific" ASM hyperresponsiveness, characteristic of asthma, involves cADPr-mediated calcium release.
Purpose of the Study:
- To investigate the role of cyclic ADP-ribose (cADPr) in airway smooth muscle (ASM) cell calcium signaling.
- To explore the contribution of cADPr and other signaling molecules (Rho/Rho kinase, phosphodiesterase) to bronchial hyperresponsiveness.
- To identify potential novel therapeutic targets for controlling bronchial hyperresponsiveness.
Main Methods:
- Investigated agonist-induced calcium responses in ASM cells.
- Examined the role of cADPr in cytokine-treated cells exhibiting increased ASM responsiveness.
- Considered the involvement of Rho/Rho kinase and phosphodiesterase signaling pathways.
Main Results:
- Cyclic ADP-ribose (cADPr) modulates agonist-induced calcium responses in airway smooth muscle (ASM) cells.
- cADPr-mediated calcium release contributes to the increased ASM responsiveness seen in cytokine-treated cells, a feature of asthma.
- Other signaling molecules like Rho/Rho kinase and phosphodiesterase also play a role in bronchial hyperresponsiveness.
Conclusions:
- Understanding signaling molecules that affect ASM calcium signaling and contractility is key.
- cADPr is implicated in the pathophysiology of airway diseases like asthma.
- Further research into these pathways could lead to new therapeutic strategies for bronchial hyperresponsiveness.
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