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Research ArticleCELLULAR AND MOLECULAR

P2Y13: Identification and Characterization of a Novel Gαi-Coupled ADP Receptor from Human and Mouse

Fang L. Zhang, Lin Luo, Eric Gustafson, Kyle Palmer, Xudong Qiao, Xuedong Fan, Shijun Yang, Thomas M. Laz, Marvin Bayne and Frederick Monsma Jr.
Journal of Pharmacology and Experimental Therapeutics May 2002, 301 (2) 705-713; DOI: https://doi.org/10.1124/jpet.301.2.705
Fang L. Zhang
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Lin Luo
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Eric Gustafson
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Kyle Palmer
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Xudong Qiao
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Xuedong Fan
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Shijun Yang
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Thomas M. Laz
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Marvin Bayne
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Frederick Monsma Jr.
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Abstract

We have identified an orphan G protein-coupled receptor, SP174, that shares a high degree of homology with the recently described ADP receptor P2Y12. mRNA for SP174 is abundant in the brain and in cells of the immune system. In the present study, we demonstrate that SP174 is also a receptor for ADP, which is coupled to Gαi. ADP potently stimulates SP174 with an EC50 of 60 nM, and other related nucleotides are active as well, with a rank order of potency 2-methylthio-ADP tetrasodium = adenosine 5′-O-2-(thio)diphosphate = 2-methylthio-ATP tetrasodium > ADP > AP3A >ATP > IDP. This pharmacological profile is similar to that for P2Y12. We have also identified the murine homolog of SP174, which exhibits 75% homology to the human receptor. ADP is also a potent agonist at the murine receptor, and its pharmacological profile is similar to its human counterpart, but ADP and related nucleotides are more potent at the murine receptor than the human receptor. In keeping with the general nomenclature for the purinergic receptors, we propose designating this novel receptor P2Y13.

Footnotes

  • This research was funded entirely by Schering-Plough Corporation. While this manuscript was in preparation, a similar study appeared in the Journal of Biological Chemistry online by Communi et al. (2001) (August 23, 2001). The receptor GPR86 (or GPR94) described in this study is identical to SP174.

  • Abbreviations:
    PLC
    phospholipase C
    GPCR
    G protein-coupled receptor
    2-MeS-ATP
    2-methylthio-ATP tetrasodium
    RT-PCR
    reverse transcription-polymerase chain reaction
    HEK
    human embryonic kidney
    PCR
    polymerase chain reaction
    HA
    hemagglutinin
    Th
    T helper
    IL
    interleukin
    FLIPR
    fluorometric image plate reader
    2-MeS-ADP
    2-methylthio-ADP tetrasodium
    ADPβS
    adenosine 5′-O-2-(thio)diphosphate
    MRS-2179
    2′-deoxy-N6-methyladenosine-3′,5′-diphosphate
    AP3A
    diadenosine triphosphate
    • Received October 29, 2002.
    • Accepted January 28, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 301 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 2
1 May 2002
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Research ArticleCELLULAR AND MOLECULAR

P2Y13: Identification and Characterization of a Novel Gαi-Coupled ADP Receptor from Human and Mouse

Fang L. Zhang, Lin Luo, Eric Gustafson, Kyle Palmer, Xudong Qiao, Xuedong Fan, Shijun Yang, Thomas M. Laz, Marvin Bayne and Frederick Monsma
Journal of Pharmacology and Experimental Therapeutics May 1, 2002, 301 (2) 705-713; DOI: https://doi.org/10.1124/jpet.301.2.705

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Research ArticleCELLULAR AND MOLECULAR

P2Y13: Identification and Characterization of a Novel Gαi-Coupled ADP Receptor from Human and Mouse

Fang L. Zhang, Lin Luo, Eric Gustafson, Kyle Palmer, Xudong Qiao, Xuedong Fan, Shijun Yang, Thomas M. Laz, Marvin Bayne and Frederick Monsma
Journal of Pharmacology and Experimental Therapeutics May 1, 2002, 301 (2) 705-713; DOI: https://doi.org/10.1124/jpet.301.2.705
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