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J Biol Chem, Vol. 275, Issue 16, 11735-11739, April 21, 2000
From the Department of Pharmacology, University of California, San
Diego, La Jolla, California 92093-0636
The determinants of "basal" activity of
signaling pathways regulating cellular responses are poorly defined.
One possibility is that cells release factors to establish the
set-point of such pathways. Here we show that treatment of Madin-Darby
canine kidney cells with the nucleotidase apyrase decreases basal
arachidonic acid release and cAMP production 30-40% and that
inhibitors of P2Y receptor action also affect basal and
forskolin-stimulated cAMP accumulation. Changing medium prominently
increases extracellular levels of ATP in Madin-Darby canine kidney,
COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely
occurs in virtually every experimental protocol with cultured cells,
implicating such release and P2Y receptor activation as critical in
establishing the set-point for signal transduction pathways.
Cellular Release of and Response to ATP as Key Determinants
of the Set-Point of Signal Transduction Pathways*
,
*
This work was supported by research and training grants from
the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Pharmacology,
0636, University of California, San Diego, La Jolla, CA 92093-0636. Tel.: 858-534-7461; Fax: 858-822-1007; E-mail: rostrom@ucsd.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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