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Molecular Pharmacology

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Research ArticleArticle

Activation of UTP-Sensitive P2Y2 Receptor Induces the Expression of Cholinergic Genes in Cultured Cortical Neurons: A Signaling Cascade Triggered by Ca2+ Mobilization and Extracellular Regulated Kinase Phosphorylation

Roy C. Y. Choi, Glanice K. Y. Chu, Nina L. Siow, Amanda W. Y. Yung, Lisa Y. Yung, Pinky S. C. Lee, Christopher C. W. Lo, Joseph Simon, Tina T. X. Dong, Eric A. Barnard and Karl W. K. Tsim
Molecular Pharmacology July 2013, 84 (1) 50-61; DOI: https://doi.org/10.1124/mol.112.084160
Roy C. Y. Choi
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Glanice K. Y. Chu
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Nina L. Siow
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Amanda W. Y. Yung
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Lisa Y. Yung
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Pinky S. C. Lee
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Christopher C. W. Lo
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Joseph Simon
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Tina T. X. Dong
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Eric A. Barnard
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Karl W. K. Tsim
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China (R.C.Y.C., G.K.Y.C., N.L.S., A.W.Y.Y., L.Y.Y., P.S.C.L., C.C.W.L., T.T.X.D., K.W.K.T.); and Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom (J.S., E.A.B.)
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Abstract

ATP functions as an extracellular signaling molecule that is costored and coreleased with neurotransmitters at central and peripheral neuronal synapses. Stimulation by ATP upregulates the expression of synaptic genes in muscle—including the genes for nicotine acetylcholine receptor (α-, δ-, and ε-subunits) and acetylcholinesterase (AChE)—via the P2Y receptor (P2YR), but the trophic response of neurons to the activation of P2YRs is less well understood. We reported that cultured cortical neurons and the developing rat brain expressed different types of P2YRs, and among these the UTP-sensitive P2Y2R was the most abundant. P2Y2R was found to exist in membrane rafts and it colocalized with the postsynaptic protein PSD-95 in cortical neurons. Notably, agonist-dependent stimulation of P2Y2R elevated the neuronal expression of cholinergic genes encoding AChE, PRiMA (an anchor for the globular form AChE), and choline acetyltransferase, and this induction was mediated by a signaling cascade that involved Ca2+ mobilization and extracellular regulated kinases 1/2 activation. The importance of P2Y2R action was further shown by the receptor’s synergistic effect with P2Y1R in enhancing cholinergic gene expression via the robust stimulation of Ca2+ influx. Taken together our results revealed a developmental function of P2Y2R in promoting synaptic gene expression and demonstrated the influence of costimulation of P2Y1R and P2Y2R in neurons.

Footnotes

    • Received November 29, 2012.
    • Accepted April 16, 2013.
  • This research was supported by the Research Grants Council of Hong Kong [Grants 660409 and 660411 (to R.C.Y.C.), and 662911 and 663012 (to K.W.K.T.)]; and TUYF Charitable Trust of Hong Kong [TUYF12SC02] (to R.C.Y.C.) and [TUYF12SC03] (to K.W.K.T.).

  • dx.doi.org/10.1124/mol.112.084160.

  • ↵Embedded ImageThis article has supplemental material available at molpharm.aspetjournals.org.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 84 (1)
Molecular Pharmacology
Vol. 84, Issue 1
1 Jul 2013
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Research ArticleArticle

Postsynaptic P2Y2 Receptor Signaling in Neurons

Roy C. Y. Choi, Glanice K. Y. Chu, Nina L. Siow, Amanda W. Y. Yung, Lisa Y. Yung, Pinky S. C. Lee, Christopher C. W. Lo, Joseph Simon, Tina T. X. Dong, Eric A. Barnard and Karl W. K. Tsim
Molecular Pharmacology July 1, 2013, 84 (1) 50-61; DOI: https://doi.org/10.1124/mol.112.084160

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Research ArticleArticle

Postsynaptic P2Y2 Receptor Signaling in Neurons

Roy C. Y. Choi, Glanice K. Y. Chu, Nina L. Siow, Amanda W. Y. Yung, Lisa Y. Yung, Pinky S. C. Lee, Christopher C. W. Lo, Joseph Simon, Tina T. X. Dong, Eric A. Barnard and Karl W. K. Tsim
Molecular Pharmacology July 1, 2013, 84 (1) 50-61; DOI: https://doi.org/10.1124/mol.112.084160
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