Chapter

Purinergic Regulation of Respiratory Diseases

Volume 55 of the series Subcellular Biochemistry pp 1-15

Date:

Nucleotide Release by Airway Epithelia

  • Eduardo R. LazarowskiAffiliated withCystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina Email author 
  • , Juliana I. SesmaAffiliated withCystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina
  • , Lucia SeminarioAffiliated withCystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina
  • , Charles R. EstherJr.Affiliated withPediatric Pulmonology, University of North Carolina
  • , Silvia M. KredaAffiliated withCystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina

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Abstract

The purinergic events regulating the airways’ innate defenses are initiated by the release of purines from the epithelium, which occurs constitutively and is enhanced by chemical or mechanical stimulation. While the external triggers have been reviewed exhaustively, this chapter focuses on current knowledge of the receptors and signaling cascades mediating nucleotide release. The list of secreted purines now includes ATP, ADP, AMP and nucleotide sugars, and involves at least three distinct mechanisms reflecting the complexity of airway epithelia. First, the constitutive mechanism involves ATP translocation to the ER/Golgi complex as energy source for protein folding, and fusion of Golgi-derived vesicles with the plasma membrane. Second, goblet cells package ATP with mucins into granules, which are discharged in response to P2Y2R activation and Ca2+-dependent signaling pathways. Finally, non-mucous cells support a regulated mechanism of ATP release involving protease activated receptor (PAR)-elicited G12/13 activation, leading to the RhoGEF-mediated exchange of GDP for GTP on RhoA, and cytoskeleton rearrangement. Together, these pathways provide fine tuning of epithelial responses regulated by purinergic signaling events.

Keywords

ATP release Airway epithelia Ectonucleotidase Thrombin Mucin