Cellular release of and response to ATP as key determinants of the set-point of signal transduction pathways.
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.
Ostrom
R S
RS
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0636, USA. rostrom@ucsd.edu
Gregorian
C
C
Insel
P A
PA
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001081:Apyrase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D018048:Receptors, Purinergic P2; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D001081:Apyrase