Differential sensitivity of human platelet P2X1 and P2Y1 receptors to disruption of lipid rafts.
ATP-stimulated P2X1 and ADP-stimulated P2Y1 receptors play important roles in platelet activation. An increase in intracellular Ca2+ represents a key signalling event coupled to both of these receptors, mediated via direct gating of Ca2+-permeable channels in the case of P2X1 and phospholipase-C-dependent Ca2+ mobilisation for P2Y1. We show that disruption of cholesterol-rich membrane lipid rafts reduces P2X1 receptor-mediated calcium increases by approximately 80%, while P2Y1 receptor-dependent Ca2+ release is unaffected. In contrast to artery, vas deferens, bladder smooth muscle, and recombinant expression in cell lines, where P2X1 receptors show almost exclusive association with lipid rafts, only approximately 20% of platelet P2X1 receptors are co-expressed with the lipid raft marker flotillin-2. We conclude that lipid rafts play a significant role in the regulation of P2X1 but not P2Y1 receptors in human platelets and that a reserve of non-functional P2X1 receptors may exist.
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK.
Catherine
C
Vial
C Y Eleanor
CY
Fung
Alison H
AH
Goodall
Martyn P
MP
Mahaut-Smith
Richard J
RJ
Evans
D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004056:Differential Threshold / Q000502:physiology*; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology*; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1
C546382:P2RY1 protein, human; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D002118:Calcium