Purinoceptor activation of chloride transport in cystic fibrosis and CFTR‐transfected pancreatic cell lines

The regulation of chloride efflux from cystic fibrosis pancreatic adenocarcinoma cells (CFPAC‐1) and wild‐type CFTR‐transfected CFPAC‐1 cells (TPAC) was compared. Forskolin (10 μ M ) stimulated chloride efflux from the corrected TPAC cells but not from CFPAC‐1 cells. Chloride efflux from both cell types was activated by thapsigargin (0.5 μ M ). The nucleotides ATP and UTP and the non‐hydrolyzable ATP analogue, adenosine 5′‐O‐(3‐thio) triphosphate (ATPγS), stimulated chloride efflux from both cell types. None of the other P 2 purinoceptor agonists investigated elicited a response. The order of potency was ATPUTPATPγS. Adenosine (10–100 μ M ) activated choride efflux from the TPAC but not the CFPAC cell line with no increase in intracellular cyclic AMP. Small but statistically significant inhibitions of the adenosine‐(50 μ M )‐stimulated increase in chloride efflux were elicited by the A 1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (CPX, 100 n M ) and the A 2 receptor antagonist 3,7‐dimethyl‐1‐propylargylxanthine (DMPX, 10 μ M ). The A 2A receptor antagonist 8‐(3‐chlorostyryl)caffeine (CSC, 100 n M ) had no significant effect. These results provide evidence for the regulation of chloride efflux by P2Y 2 purinoceptors in genetically‐corrected and CF pancreatic cell lines. Studies with adenosine receptor antagonists indicate some possible involvement of A 1 and A 2 (but not A 2A ) receptors in the adenosine stimulation of chloride efflux, but the relatively small effects of the inhibitors coupled with lack of increase in cyclic AMP and a response only in the CFTR‐transfected cells also suggests a possible direct effect of adenosine on CFTR.British Journal of Pharmacology (1998) 124 , 1597–1606; doi: 10.1038/sj.bjp.0701990