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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-02-0642.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1400-1408
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Immunolocalization of P2Y1 and TP receptors in
platelets showed a major pool associated with the membranes of
-granules and the open canalicular system
Paquita Nurden,
Christel Poujol,
Joelle Winckler,
Robert Combrié,
Nathalie Pousseau,
Pamela B. Conley,
Sylviane Levy-Toledano,
Aida Habib, and
Alan T. Nurden
From Centre National de la Recherche Scientifique
(CNRS), Hôpital Cardiologique, Pessac,
France; COR Millennium, South San Francisco, CA; and
Institut National de la Santé et de la Recherche Médicale
(INSERM) U 348, Hôpital Laribosière, Paris,
France.
P2Y1 and thromboxane-prostanoid- (TP)
receptors on platelets belong to the G-protein-coupled
7-transmembrane domain family. They transmit signals for shape change,
mobilization of calcium, and platelet aggregation. Immunogold labeling
with a monoclonal antibody (MoAb) to the amino-terminal domain of
P2Y1 and a polyclonal antibody to the C-terminal domain of
TP revealed that while present at the platelet surface, both
receptors were abundantly represented inside the platelet.
Specifically, receptors were found in membranes of -granules and
elements of the open-canalicular system. A similar organization was
found in mature megakaryocytes. Activation of platelets by
adenosine diphosphate (ADP) and the thromboxane A2 (TXA2) analog, I-BOP [1S-(1 ,2  (5Z),3
-(1E,3S)4
)-7-(3-(3- hydroxy-4-(p-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid], increased the labeling of both P2Y1 and
TP at the surface and in intracellular pools, suggesting that
activation resulted in greater antibody accessibility to the receptor.
A return to a platelet discoid shape and to basal values of labeling
accompanied receptor desensitization. Platelets lacking the
P2Y12 ADP receptor normally expressed P2Y1 and
TP, both before and after activation. Studies with the
anti-ligand-induced binding site (anti-LIBS) MoAb,
AP-6, confirmed that stored fibrinogen associated with
internal pools of IIb3 at the start of
secretion in a microenvironment containing agonist receptors.
Pharmacologic antagonism of ADP or TXA2 receptors in
antithrombotic therapy may need to take into account blockade of
internal receptor pools.
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