CPX, a selective A1-adenosine-receptor antagonist, regulates intracellular pH in cystic fibrosis cells.
The selective A1-adenosine-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), has been reported to activate Cl- efflux from cystic fibrosis cells, such as pancreatic CFPAC-1 and lung IB3 cells bearing the cystic fibrosis transmembrane regulator(delta F508) mutation, but has little effect on the same process in cells repaired by transfection with wild-type cystic fibrosis transmembrane regulator (O. Eidelman, 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 cells repaired with the wild-type gene. CPX also mildly decreases resting intracellular pH. In CFPAC-1 cells, this downregulation is dependent on the presence of adenosine, since pretreatment of the cells with adenosine deaminase blocks the CPX effect. We also show that, by contrast, CPX action on these cells does not lead to alterations in intracellular free Ca2+ concentration. We conclude that CPX affects pH regulation in CFPAC-1 cells, probably by antagonizing the tonic action of endogenous adenosine.
Casavola
V
V
Laboratory of Cell Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Turner
R J
RJ
Guay-Broder
C
C
Jacobson
K A
KA
Eidelman
O
O
Pollard
H B
HB
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D009994:Osmolar Concentration; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014162:Transfection; D014970:Xanthines / Q000494:pharmacology*
C505032:CFTR protein, human; D008565:Membrane Proteins; D058915:Purinergic P1 Receptor Antagonists; D017923:Sodium-Hydrogen Exchangers; D014970:Xanthines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C051360:1,3-dipropyl-8-cyclopentylxanthine; D002118:Calcium