QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 1, 2003, 23(11):4437-4444

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (35) Citing Articles via Google Scholar Google Scholar Articles by Fam, S. R. Articles by Salter, M. W. Search for Related Content PubMed PubMed Citation Articles by Fam, S. R. Articles by Salter, M. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL

 Previous Article  |  Next Article 

Differential Frequency Dependence of P2Y₁- and P2Y₂- Mediated Ca ²⁺ Signaling in Astrocytes

Sami R. Fam,^1,2 Conor J. Gallagher,^1,3 Lorraine V. Kalia,^1,3 and Michael W. Salter^1,2,3

¹ Programme in Brain and Behaviour, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8, ² Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5G 1X8, and ³ Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5G 1X8

ATP is a key extracellular messenger that mediates the propagation of Ca ²⁺ waves in astrocyte networks in various regions of the CNS. ATP-mediated Ca ²⁺ signals play critical roles in astrocyte proliferation and differentiation and in modulating neuronal activity. The actions of ATP on astrocytes are via two distinct subtypes of P2Y purinoceptors, P2Y₁ and P2Y₂ receptors (P2Y₁Rs and P2Y₂Rs), G-protein coupled receptors that stimulate mobilization of intracellular Ca ²⁺ ([Ca ²⁺]_i) via the phospholipase C-IP₃ pathway. We report here that P2Y₁R-mediated and P2Y₂R-mediated Ca ²⁺ responses differentially show two forms of activity-dependent negative feedback. First, Ca ²⁺ responses mediated by either receptor exhibit slow depression that is independent of stimulation frequency. Second, responses mediated by P2Y₁Rs, but not those mediated by P2Y₂Rs, show rapid oscillations after high-frequency stimulation. We demonstrate that the oscillations are mediated by recruiting negative feedback by protein kinase C, and we map the site responsible for the effect of protein kinase C to Thr³³⁹ in the C terminus of P2Y₁R. We propose that frequency-dependent changes in ATP-mediated Ca ²⁺ signaling pathways may modulate astrocyte function and astrocyte–neuron signaling in the CNS.

Key words: P2Y₁; P2Y₂; PKC; frequency; astrocytes; ATP; Ca ²⁺ signaling

---

Received Oct. 18, 2002; revised Mar. 7, 2003; accepted Mar. 12, 2003.

This article has been cited by other articles:

				S. Reiner, N. Ziegler, C. Leon, K. Lorenz, K. von Hayn, C. Gachet, M. J. Lohse, and C. Hoffmann {beta}-Arrestin-2 Interaction and Internalization of the Human P2Y1 Receptor Are Dependent on C-Terminal Phosphorylation Sites Mol. Pharmacol., December 1, 2009; 76(6): 1162 - 1171. [Abstract] [Full Text] [PDF]

				I. Grimm, N. Messemer, M. Stanke, C. Gachet, and H. Zimmermann Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells J. Cell Sci., July 15, 2009; 122(14): 2524 - 2533. [Abstract] [Full Text] [PDF]

				R. C. Y. Choi, J. Simon, K. W. K. Tsim, and E. A. Barnard Constitutive and Agonist-induced Dimerizations of the P2Y1 Receptor: RELATIONSHIP TO INTERNALIZATION AND SCAFFOLDING J. Biol. Chem., April 18, 2008; 283(16): 11050 - 11063. [Abstract] [Full Text] [PDF]

				M. Domercq, L. Brambilla, E. Pilati, J. Marchaland, A. Volterra, and P. Bezzi P2Y1 Receptor-evoked Glutamate Exocytosis from Astrocytes: CONTROL BY TUMOR NECROSIS FACTOR-{alpha} AND PROSTAGLANDINS J. Biol. Chem., October 13, 2006; 281(41): 30684 - 30696. [Abstract] [Full Text] [PDF]

				S. J. Mundell, M. L. Jones, A. R. Hardy, J. F. Barton, S. M. Beaucourt, P. B. Conley, and A. W. Poole Distinct Roles for Protein Kinase C Isoforms in Regulating Platelet Purinergic Receptor Function Mol. Pharmacol., September 1, 2006; 70(3): 1132 - 1142. [Abstract] [Full Text] [PDF]

				S. R. Fam, M. Paquet, A. M. Castleberry, H. Oller, C. J. Lee, S. F. Traynelis, Y. Smith, C. C. Yun, and R. A. Hall P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2 PNAS, May 31, 2005; 102(22): 8042 - 8047. [Abstract] [Full Text] [PDF]

				A. R. Hardy, P. B. Conley, J. Luo, J. L. Benovic, A. W. Poole, and S. J. Mundell P2Y1 and P2Y12 receptors for ADP desensitize by distinct kinase-dependent mechanisms Blood, May 1, 2005; 105(9): 3552 - 3560. [Abstract] [Full Text] [PDF]

				M. Weick, P. Wiedemann, A. Reichenbach, and A. Bringmann Resensitization of P2Y Receptors by Growth Factor-Mediated Activation of the Phosphatidylinositol-3 Kinase in Retinal Glial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1525 - 1532. [Abstract] [Full Text] [PDF]

				A. Baurand, A. Eckly, B. Hechler, G. Kauffenstein, J.-L. Galzi, J.-P. Cazenave, C. Leon, and C. Gachet Differential Regulation and Relocalization of the Platelet P2Y Receptors after Activation: A Way to Avoid Loss of Hemostatic Properties? Mol. Pharmacol., March 1, 2005; 67(3): 721 - 733. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help