AJP - Cell Physiology, Vol 265, Issue 3 C577-C606, Copyright © 1993 by American Physiological Society

ARTICLES

Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides

G. R. Dubyak and C. el-Moatassim
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.

Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5'-nucleotidases. The diverse biological responses to ATP are mediated by a variety of cell surface receptors that are activated when ATP or other nucleotides are bound. The functionally identified nucleotide or P2-purinergic receptors include 1) ATP receptors that stimulate G protein-coupled effector enzymes and signaling cascades, including inositol phospholipid hydrolysis and the mobilization of intracellular Ca2+ stores; 2) ATP receptors that directly activate ligand-gated cation channels in the plasma membranes of many excitable cell types; 3) ATP receptors that, via the rapid induction of surface membrane channels and/or pores permeable to ions and endogenous metabolites, produce cytotoxic or activation responses in macrophages and other immune effector cells; and 4) ADP receptors that trigger rapid ion fluxes and aggregation responses in platelets. Current research in this area is directed toward the identification and structural characterization of these receptors by biochemical and molecular biological approaches.

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				D.-M. Zhao, H.-H. Xue, K. Chida, T. Suda, Y. Oki, M. Kanai, C. Uchida, A. Ichiyama, and H. Nakamura Effect of erythromycin on ATP-induced intracellular calcium response in A549 cells Am J Physiol Lung Cell Mol Physiol, April 1, 2000; 278(4): L726 - L736. [Abstract] [Full Text] [PDF]

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				J. Sevigny, S. C. Robson, E. Waelkens, E. Csizmadia, R. N. Smith, and R. Lemmens Identification and Characterization of a Novel Hepatic Canalicular ATP Diphosphohydrolase J. Biol. Chem., February 25, 2000; 275(8): 5640 - 5647. [Abstract] [Full Text] [PDF]

				H. J. Agteresch, P. C. Dagnelie, A. van der Gaast, T. Stijnen, and J. H. P. Wilson Randomized Clinical Trial of Adenosine 5'-Triphosphate in Patients With Advanced Non-Small-Cell Lung Cancer J Natl Cancer Inst, February 16, 2000; 92(4): 321 - 328. [Abstract] [Full Text] [PDF]

				K. Koziak, E. Kaczmarek, A. Kittel, J. Sevigny, J. K. Blusztajn, J. Schulte am Esch II, M. Imai, O. Guckelberger, C. Goepfert, I. Qawi, et al. Palmitoylation Targets CD39/Endothelial ATP Diphosphohydrolase to Caveolae J. Biol. Chem., January 21, 2000; 275(3): 2057 - 2062. [Abstract] [Full Text] [PDF]

				J. S. Glavy, S. M. Wu, P. J. Wang, G. A. Orr, and A. W. Wolkoff Down-regulation by Extracellular ATP of Rat Hepatocyte Organic Anion Transport Is Mediated by Serine Phosphorylation of Oatp1 J. Biol. Chem., January 14, 2000; 275(2): 1479 - 1484. [Abstract] [Full Text] [PDF]

				D. J. Kusner and J. Adams ATP-Induced Killing of Virulent Mycobacterium tuberculosis Within Human Macrophages Requires Phospholipase D J. Immunol., January 1, 2000; 164(1): 379 - 388. [Abstract] [Full Text] [PDF]

				M. A. Balboa, J. Balsinde, C. A. Johnson, and E. A. Dennis Regulation of Arachidonic Acid Mobilization in Lipopolysaccharide-activated P388D1 Macrophages by Adenosine Triphosphate J. Biol. Chem., December 17, 1999; 274(51): 36764 - 36768. [Abstract] [Full Text] [PDF]

				J. van Baal, J. G. J. Hoenderop, M. Groenendijk, C. H. van Os, R. J. M. Bindels, and P. H. G. M. Willems Hormone-stimulated Ca2+ transport in rabbit kidney: multiple sites of inhibition by exogenous ATP Am J Physiol Renal Physiol, December 1, 1999; 277(6): F899 - F906. [Abstract] [Full Text] [PDF]

				S. Rounds, L. L. Likar, E. O. Harrington, K. C. Kim, A. Smeglin, K. Heins, and N. Parks Nucleotide-induced PMN adhesion to cultured epithelial cells: possible role of MUC1 mucin Am J Physiol Lung Cell Mol Physiol, November 1, 1999; 277(5): L874 - L880. [Abstract] [Full Text] [PDF]

				K.-I. Hosoya, H. Ueda, K.-J. Kim, and V. H. L. Lee Nucleotide Stimulation of Cl- Secretion in the Pigmented Rabbit Conjunctiva J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 53 - 59. [Abstract] [Full Text]

				O. Zaborina, N. Misra, J. Kostal, S. Kamath, V. Kapatral, M. E.-A. El-Idrissi, B. S. Prabhakar, and A. M. Chakrabarty P2Z-Independent and P2Z Receptor-Mediated Macrophage Killing by Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients Infect. Immun., October 1, 1999; 67(10): 5231 - 5242. [Abstract] [Full Text] [PDF]

				W. P. Schilling, W. G. Sinkins, and M. Estacion Maitotoxin activates a nonselective cation channel and a P2Z/P2X7-like cytolytic pore in human skin fibroblasts Am J Physiol Cell Physiol, October 1, 1999; 277(4): C755 - C765. [Abstract] [Full Text] [PDF]

				W. P. Schilling, T. Wasylyna, G. R. Dubyak, B. D. Humphreys, and W. G. Sinkins Maitotoxin and P2Z/P2X7 purinergic receptor stimulation activate a common cytolytic pore Am J Physiol Cell Physiol, October 1, 1999; 277(4): C766 - C776. [Abstract] [Full Text] [PDF]

				D. E. McCoy, A. L. Taylor, B. A. Kudlow, K. Karlson, M. J. Slattery, L. M. Schwiebert, E. M. Schwiebert, and B. A. Stanton Nucleotides regulate NaCl transport in mIMCD-K2 cells via P2X and P2Y purinergic receptors Am J Physiol Renal Physiol, October 1, 1999; 277(4): F552 - F559. [Abstract] [Full Text] [PDF]

				L. Homolya, W. C. Watt, E. R. Lazarowski, B. H. Koller, and R. C. Boucher Nucleotide-regulated Calcium Signaling in Lung Fibroblasts and Epithelial Cells from Normal and P2Y2 Receptor (-/-) Mice J. Biol. Chem., September 10, 1999; 274(37): 26454 - 26460. [Abstract] [Full Text] [PDF]