Coupling of airway ciliary activity and mucin secretion to mechanical stresses by purinergic signaling

The mucociliary clearance system is comprised of three components, ion transport activities controlling the height of airway surface liquid (ASL), mucin secretion, and ciliary activity. These activities in humans are controlled principally by local agonists, extracellular nucleotides and nucleosides released from the epithelium. Importantly, mechanical stresses stimulate goblet cell mucin secretion, ciliary beating, and Cl- and fluid secretion through mechanically induced nucleotide release. Emerging evidence also implicates co-secretion of nucleotides and mucin from goblet cells as a source of extracellular agonist. At rest, ATP is released onto airway surfaces at similar to 370 fmol/min cm(2), but only similar to 3% of released ATP is recovered in ASL Secreted UTP meets with a similar fate. A wide variety of hydrolytic and transphosphorylating ectoenzymes convert the triphosphate nucleotides into ADP, AMP, and adenosine, UDR UMP, and uridine. Of these, ATP, adenosine. UTP, and UDP act as agonists at apical P2Y(2) (ATP, UTP), P2Y(6) (UDP). and A(2B) (adenosine) receptors on ciliated and/or goblet cells to regulate mucociliary clearance. (C) 2008 Elsevier B.V. All rights reserved.