Cpx, a selective a1 adenosine receptor antagonist, regulates intracellular
ph in cystic fibrosis cells..
Casavola, Valeria, R. James Turner, Colleen Guay-Broder, Kenneth A. Jacobson,
Ofer Eidelman, and Harvey B. Pollard.
Laboratory of Cell Biology and Genetics, National Institute of Diabetes,
Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8, Rm.
401, Bethesda, MD 20892; Laboratory of Bioorganic Chemistry, National
Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of
Health, Bldg. 8, Rm., B1A17, Bethesda, MD 20892; Clinical Investigations and
Patient Care Branch, National Institute of Dental Research, National
Institutes of Health, Bldg. 10, Rm. 1A06, Bethesda, MD 20892; Istituto Di
Fisiologia Generale, Universit[acute]a Degli Studi di Bari, Via Amendola 165/A,
70126 Bari, ITALY.
APStracts 2:0073C, 1995.
The A1-selective adenosine receptor antagonist CPX has been reported to
activate chloride efflux from cystic fibrosis cells such as pancreatic CFPAC
-1 and lung IB3 cells bearing the CFTR(F508) mutation, but has little effect
on the same process in cells repaired by transfection with wild type CFTR
(Eidelman, et al 1992 PNAS 89:5562-5566). We report here that CPX down
-regulates 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 pHi. In CFPAC-1 cells, this down-regulation is dependent upon 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+]. We conclude that CPX affects pH regulation in CFPAC-1 cells,
probably by antagonizing the tonic action of endogenous adenosine.
Received 18 April 1994; accepted in final form 13 January 1995.
APS Manuscript Number C205-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.