Cellular atp release by the cystic fibrosis transmembrane
conductance regulator.
Prat, Adriana G., Ignacio L. Reisin, Dennis A. Ausiello, and Horacio
F. Cantiello.
Renal Unit, Massachusetts General Hospital East, Charlestown, MA,
and Department of Medicine, Harvard Medical School, Boston, MA
APStracts 2:0310C, 1995.
Recent studies from our laboratory indicate that members of the ATP
-binding cassette (ABC) family of transporters, including P
-glycoprotein and cystic fibrosis transmembrane conductance regulator
(CFTR), are ATP-permeable channels. The physiological relevance of
this novel transport mechanism is largely unknown. In the present
study, intra- and extracellular ATP content, cellular ATP release and
oxygen consumption before and after cAMP-stimulation were determined
to assess the role of CFTR in the transport of ATP under
physiological conditions. The functional expression of CFTR by the
stable transfection of mouse mammary carcinoma cells, C127i, with
human epithelial CFTR-cDNA resulted in an stimulated metabolism since
both basal and cAMP-inducible oxygen consumption were increased as
compared to mock-transfected cells. The stimulated (but not basal)
oxygen consumption was inhibited by diphenyl-2-carboxylic acid (DPC),
a known inhibitor of CFTR. CFTR-expression was also associated with
the cAMP-activated and DPC-inhibitable release of intracellular ATP.
The recovery of intracellular ATP from complete depletion after
metabolic poisoning was also assessed under basal and cAMP-stimulated
conditions. The various maneuvers indicate that CFTR may be an
important contributor to the release of cellular ATP which may help
modify signal transduction pathways associated with secretory Cl-
movement or other related processes. Changes in the CFTR-mediated
delivery of nucleotides to the extracellular compartment may play an
important role in the onset and reversal of the cystic fibrosis
phenotype.
Received 4 April 1995; accepted in final form 18 August 1995.
APS Manuscript Number C194-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.