CPX, A SELECTIVE A(1)-ADENOSINE-RECEPTOR ANTAGONIST, REGULATES INTRACELLULAR PH IN CYSTIC-FIBROSIS CELLS

The selective A(1)-adenosine-receptor antagonist, 8-cyclopentyl-1,3-di propylxanthine (CPX), has been reported to activate Cl- efflux from cy stic fibrosis cells, such as pancreatic CFPAC-1 and lung IB3 cells bea ring the cystic fibrosis transmembrane regulator(Delta F508) mutation, but has little effect on the same process in cells repaired by transf ection with wild-type cystic fibrosis transmembrane regulator (O. Eide lman, C. Guay-Broder, P. J. M, van Galen, K. A. Jacobson, C. Fox, R. J . Turner, Z. I. Cabantchik, and H. B. Pollard. Proc. Natl. Acad. Sci. USA 89: 5562-5566, 1992). We report here that CPX downregulates Na+/H exchange activity in CFPAC-1 cells but has a much smaller effect on c ells repaired with the wild-type gene. CPX also mildly decreases resti ng intracellular pH. In CFPAC-1 cells, this downregulation is dependen t on the presence of adenosine, since pretreatment of the cells with a denosine deaminase blocks the CPX effect. We also show that, by contra st, CPX action on these cells does not lead to alterations in intracel lular free Ca2+ concentration. We conclude that CPX affects pH regulat ion in CFPAC-1 cells, probably by antagonizing the tonic action of end ogenous adenosine.