REGULATION OF TRANSEPITHELIAL ION-TRANSPORT AND INTRACELLULAR CALCIUM BY EXTRACELLULAR ATP IN HUMAN NORMAL AND CYSTIC-FIBROSIS AIRWAY EPITHELIUM

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 (UPT greater-than-or-equal-to ATP > ATP-gamma-S > 2MeSATP > ADP-beta-S >> beta-gamma-MeATP greater-than-or-equal-to alpha-beta-MeATP) or basolateral membrane (2MeSATP > UTP > ATP > ATP-gamma-S > alpha-beta-MeATP > beta-gamma-MeATP) 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 greater-than-or-equal-to 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.