The P2Y2 receptor coordinates the entire mechanism of mucociliary clearance in the upper and lower respiratory tract. This process can be regulated therapeutically by the local delivery of molecules that bind to and activate the receptors. Studies have established that P2Y2 receptors are found on each of the three principal cell types that line the airways: ciliated epithelial cells; goblet cells; and Type II alveolar cells. On activation of the P2Y2 receptor on ciliated epithelial cells, salt and water are released from the cell, mucous secretions are hydrated, and ciliary beat frequency is increased. Activation of the P2Y2 receptor on goblet cells modulates the release of mucin. When the P2Y2 receptors on Type II alveolar cells are activated, they release surfactant, a lubricating molecule that maintains the surface tension of the smallest peripheral airways and prevents their collapse.
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EPITHELIAL CELL... |
GOBLET CELL... |
TYPE II ALVEOLAR CELL... |
P2Y2 receptors are present on three types of human airway cells: |
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The ability to activate mucosal hydration and mucociliary clearance in the lungs and upper airways provides opportunities for the treatment of serious disorders including cystic fibrosis, a fatal genetic disease, as well as upper respiratory disorders that involve nasal symptoms such as congestion, pressure and nasal blockage. Such disorders include rhinosinusitis, allergic rhinitis and upper respiratory infections including the common cold and influenza. In addition, increasing mucociliary clearance in the lungs allows for non-invasive collection of mucus samples from the lungs which may be beneficial in the diagnosis of lung cancer.
Denufosol tetrasodium inhalation solution for cystic fibrosis - Phase 3
(diquafosol tetrasodium ophthalmic solution) 2% for dry eye - Phase 3; Approvable
(azithromycin ophthalmic solution) 1% for blepharitis - Phase 2
INS115644 and INS117548 for glaucoma - Phase 1
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