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Molecular Pharmacology

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Research ArticleORIGINAL ARTICLE

Differential Regulation and Relocalization of the Platelet P2Y Receptors after Activation: A Way to Avoid Loss of Hemostatic Properties?

Anthony Baurand, Anita Eckly, Béatrice Hechler, Gilles Kauffenstein, Jean-Luc Galzi, Jean-Pierre Cazenave, Catherine Léon and Christian Gachet
Molecular Pharmacology March 2005, 67 (3) 721-733; DOI: https://doi.org/10.1124/mol.104.004846
Anthony Baurand
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Anita Eckly
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Béatrice Hechler
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Gilles Kauffenstein
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Jean-Luc Galzi
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Jean-Pierre Cazenave
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Catherine Léon
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Christian Gachet
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Abstract

In the present study, we investigated the desensitization and trafficking of the P2Y1 and P2Y12 receptors after agonist-induced stimulation of platelets or astrocytoma cells transfected with the P2Y1 or P2Y12 receptors fused to green fluorescent protein. In platelets and in transfected cells, exposure to 10 μM ADP caused desensitization of the P2Y1 receptor-driven calcium signal, whereas the P2Y12 receptor-mediated inhibition of cAMP formation was not affected. Plasma membranes from ADP-stimulated platelets also retained P2Y12 activity. Agonist-induced P2Y1 receptor desensitization was accompanied by its internalization in platelets and transfected cells. In contrast, although a substantial fraction of P2Y12 receptors was rapidly and transiently internalized, most of the P2Y12 receptors remained at the plasma membrane. Activated P2Y1 receptors were internalized through a clathrin-dependent pathway in cells and platelets, whereas the P2Y12 receptors seemed to use a distinct, clathrin-independent pathway. Together, these data indicate that the P2Y1 and P2Y12 receptors are differentially regulated upon activation. The absence of desensitization of the Gi protein-coupled P2Y12 receptor-dependent responses could represent a mechanism to preserve the hemostatic properties of otherwise unresponsive platelets.

  • Received July 9, 2004.
  • Accepted December 14, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (3)
Molecular Pharmacology
Vol. 67, Issue 3
1 Mar 2005
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Research ArticleORIGINAL ARTICLE

Differential Regulation and Relocalization of the Platelet P2Y Receptors after Activation: A Way to Avoid Loss of Hemostatic Properties?

Anthony Baurand, Anita Eckly, Béatrice Hechler, Gilles Kauffenstein, Jean-Luc Galzi, Jean-Pierre Cazenave, Catherine Léon and Christian Gachet
Molecular Pharmacology March 1, 2005, 67 (3) 721-733; DOI: https://doi.org/10.1124/mol.104.004846

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Research ArticleORIGINAL ARTICLE

Differential Regulation and Relocalization of the Platelet P2Y Receptors after Activation: A Way to Avoid Loss of Hemostatic Properties?

Anthony Baurand, Anita Eckly, Béatrice Hechler, Gilles Kauffenstein, Jean-Luc Galzi, Jean-Pierre Cazenave, Catherine Léon and Christian Gachet
Molecular Pharmacology March 1, 2005, 67 (3) 721-733; DOI: https://doi.org/10.1124/mol.104.004846
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