Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice - PubMed (original) (raw)
Comparative Study
. 1999 Oct;5(10):1199-202.
doi: 10.1038/13522.
Affiliations
- PMID: 10502826
- DOI: 10.1038/13522
Comparative Study
Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice
J E Fabre et al. Nat Med. 1999 Oct.
Abstract
Platelet activation is characterized by shape change, induction of fibrinogen receptor expression and release of granular contents, leading to aggregation and plug formation. While this response is essential for hemostasis, it is also important in the pathogenesis of a broad spectrum of diseases, including myocardial infarction, stroke and unstable angina. Adenosine 5'-diphosphate (ADP) induces platelet aggregation, but the mechanism for this has not been established, and the relative contribution of ADP in hemostasis and the development of arterial thrombosis is poorly understood. We show here that the purinoceptor P2Y1 is required for platelet shape change in response to ADP and is also a principal receptor mediating ADP-induced platelet aggregation. Activation of P2Y1 resulted in increased intracellular calcium but no alteration in cyclic adenosine monophosphate (cAMP) levels. P2Y1-deficient platelets partially aggregated at higher ADP concentrations, and the lack of P2Y1 did not alter the ability of ADP to inhibit cAMP, indicating that platelets express at least one additional ADP receptor. In vivo, the lack of P2Y1 expression increased bleeding time and protected from collagen- and ADP-induced thromboembolism. These findings support the hypothesis that the ATP receptor P2Y1 is a principal receptor mediating both physiologic and pathological ADP-induced processes in platelets.
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