Regulation of transepithelial ion transport and intracellular calcium by extracellular ATP in human normal and cystic fibrosis airway epithelium

Abstract

1 The role of extracellular nucleotides in regulation of ion transport activities (short circuit current, I_sc) of human respiratory epithelia was studied. 2 Application of nucleotides to the apical or basolateral membrane of human nasal epithelium induced a concentration-dependent increase in I_sc. 3 The rank order of potency of purine- or pyrimidine-induced changes in I_sc of normal human nasal epithelium when applied to the apical membrane (UTP ≥ ATP > ATPγS > 2MeSATP > ADPβS ≫ βγMeATP ≥ βγMeATP) or basolateral membrane (2MeSATP > UTP > ATP > ATPγS > αβMeATP > βγMeATP) is consistent with involvement of a P₂ purinoceptor. A similar rank order of potencies was observed for nucleotide effects on intracellular calcium measured by Fura-2 fluorescence using microspectrofluorimetry. 4 Similar nucleotide potency in the regulation of ion transport and intracellular calcium in cystic fibrosis (CF) airway epithelium (UTP ≥ ATP) was observed, suggesting purinoceptors might be used to stimulate ion transport processes that would promote hydration of airway secretions and facilitate their clearance from CF lungs. 5 These data provide evidence for the regulation of ion transport by P₂ purinoceptors in normal and cystic fibrosis human airway epithelium.