AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 285: L376-L385, 2003. First published April 4, 2003; doi:10.1152/ajplung.00447.2002
1040-0605/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/2/L376    most recent
00447.2002v2
00447.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (23)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schäfer, R.
Right arrow Articles by Reiser, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schäfer, R.
Right arrow Articles by Reiser, G.

ATP- and UTP-activated P2Y receptors differently regulate proliferation of human lung epithelial tumor cells

Rainer Schäfer,1 Fariba Sedehizade,1 Tobias Welte,2 and Georg Reiser1

1Institut für Neurobiochemie and 2Klinik für Kardiologie, Angiologie, und Pneumologie, Medizinische Fakultät, Otto-von-Guericke-Universität, 39120 Magdeburg, Germany

Submitted 30 December 2002 ; accepted in final form 27 March 2003

The involvement of P2Y receptors, which are activated by extracellular nucleotides, in proliferative regulation of human lung epithelial cells is unclear. Here we show that extracellular ATP and UTP stimulate bromodeoxyuridine (BrdU) incorporation into epithelial cell lines. The nucleotide efficacy profile [ATP = ADP > UDP >= UTP > adenosine >= 2-methylthioadenosine-5'-diphosphate, with {alpha},{beta}-methylene adenosine 5'-triphosphate, 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, AMP, UMP, and ATP{alpha}S inactive] and PCR analysis indicate involvement of P2Y2 and P2Y6 receptors. The signal transduction pathway, which, via the P2Y2 receptor, transmits the proliferative activity of ATP or UTP in A549 cells downstream of phospholipase C, depends on Ca2+/calmodulin-dependent protein kinase II and nuclear factor-{kappa}B, but not on protein kinase C. Signaling does not involve the mitogen-activated protein kinases extracellular signal-regulated kinases-1 and -2, the phosphatidylinositol 3-kinase pathway, or Src kinases. Thus nucleotides regulate proliferation of human lung epithelial cells by a novel pathway. The stimulatory effect of UTP, but not ATP, in A549 cells is attenuated by preincubation with interleukin-1{beta} and interleukin-6, but not tumor ncerosis factor-{alpha}. This indicates an important role for the pyrimidine-activated P2Y receptor in the inflammatory response of lung epithelia. ATP antagonizes the antiproliferative effect of the anticancer drugs paclitaxel and etoposide, whereas it enhances the activity of cisplatin about fourfold. Thus pathways activated by extracellular nucleotides differentially control proliferation of lung epithelial tumor cells.

purinergic receptors; cancer; cytokines; extracellular nucleotides


Address for reprint requests and other correspondence: G. Reiser, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Neurobiochemie, Leipziger Str. 44, 39120 Magdeburg, Germany (E-mail: georg.reiser{at}medizin.uni-magdeburg.de).




This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
S. Buvinic, M. Bravo-Zehnder, J. L. Boyer, J. P. Huidobro-Toro, and A. Gonzalez
Nucleotide P2Y1 receptor regulates EGF receptor mitogenic signaling and expression in epithelial cells
J. Cell Sci., December 15, 2007; 120(24): 4289 - 4301.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Tatur, N. Groulx, S. N. Orlov, and R. Grygorczyk
Ca2+-dependent ATP release from A549 cells involves synergistic autocrine stimulation by coreleased uridine nucleotides
J. Physiol., October 15, 2007; 584(2): 419 - 435.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Song, S. J. Ramus, D. Shadforth, L. Quaye, S. K. Kjaer, R. A. DiCioccio, A. M. Dunning, E. Hogdall, C. Hogdall, A. S. Whittemore, et al.
Common Variants in RB1 Gene and Risk of Invasive Ovarian Cancer.
Cancer Res., October 15, 2006; 66(20): 10220 - 10226.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. Muller, H. Bayer, D. Myrtek, D. Ferrari, S. Sorichter, M. W. Ziegenhagen, G. Zissel, J. C. Virchow Jr., W. Luttmann, J. Norgauer, et al.
The P2Y14 Receptor of Airway Epithelial Cells: Coupling to Intracellular Ca2+ and IL-8 Secretion
Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 601 - 609.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
S. van Wetering, G. S. Tjabringa, and P. S. Hiemstra
Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells
J. Leukoc. Biol., April 1, 2005; 77(4): 444 - 450.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Ahmad, A. Ahmad, M. Ghosh, C. C. Leslie, and C. W. White
Extracellular ATP-mediated Signaling for Survival in Hyperoxia-induced Oxidative Stress
J. Biol. Chem., April 16, 2004; 279(16): 16317 - 16325.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.