RT Journal Article
SR Electronic
T1 Differential Regulation and Relocalization of the Platelet P2Y Receptors after Activation: A Way to Avoid Loss of Hemostatic Properties?
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 721
OP 733
DO 10.1124/mol.104.004846
VO 67
IS 3
A1 Baurand, Anthony
A1 Eckly, Anita
A1 Hechler, Béatrice
A1 Kauffenstein, Gilles
A1 Galzi, Jean-Luc
A1 Cazenave, Jean-Pierre
A1 Léon, Catherine
A1 Gachet, Christian
YR 2005
UL http://molpharm.aspetjournals.org/content/67/3/721.abstract
AB 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.