Immunolocalization of P2Y1 and TPalpha receptors in platelets showed a major pool associated with the membranes of alpha -granules and the open canalicular system.

P. Nurden
Blood. 2002-10-10; 101(4): 1400-1408
DOI: 10.1182/blood-2002-02-0642

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1. Blood. 2003 Feb 15;101(4):1400-8. Epub 2002 Oct 10.

Immunolocalization of P2Y1 and TPalpha receptors in platelets showed a major pool
associated with the membranes of alpha -granules and the open canalicular system.

Nurden P(1), Poujol C, Winckler J, Combrié R, Pousseau N, Conley PB,
Levy-Toledano S, Habib A, Nurden AT.

Author information:
(1)Centre National de la Recherche Scientifique (CNRS), Hôpital Cardiologique,
Pessac, France.

P2Y(1) and thromboxane-prostanoid-alpha (TPalpha) 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 P2Y(1)
and a polyclonal antibody to the C-terminal domain of TPalpha revealed that while
present at the platelet surface, both receptors were abundantly represented
inside the platelet. Specifically, receptors were found in membranes of
alpha-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 A(2) (TXA(2)) analog, I-BOP
[1S-(1 alpha,2 beta(5Z),3 alpha-(1E,3S)4 alpha)-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 P2Y(1) and TPalpha 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
P2Y(12) ADP receptor normally expressed P2Y(1) and TPalpha, 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
alpha(IIb)beta(3) at the start of secretion in a microenvironment containing
agonist receptors. Pharmacologic antagonism of ADP or TXA(2) receptors in
antithrombotic therapy may need to take into account blockade of internal
receptor pools.

DOI: 10.1182/blood-2002-02-0642
PMID: 12393588 [Indexed for MEDLINE]

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