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Inhibition of the platelet $P2Y_{12}$receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin
| Content Provider | Scilit |
|---|---|
| Author | Cattaneo, M. Lecchi, A. |
| Copyright Year | 2007 |
| Description | Journal: Journal of Thrombosis and Haemostasis Background: Activation of two receptors for adenosine diphosphate (ADP), $P2Y_{1}$ and $P2Y_{12}$, is necessary for ADP-induced platelet aggregation (PA). It is generally believed that the antithrombotic effects of drugs inhibiting $P2Y_{12}$, such as clopidogrel, are uniquely mediated by inhibition of $P2Y_{12}$-dependent PA. However, as $P2Y_{12}$ is negatively coupled to adenylyl cyclase (AC), its inhibition may also exert antithrombotic effects through the potentiation of prostacyclin $(PGI_{2}$), which inhibit PA by stimulating AC. Objectives: To test whether inhibition of $P2Y_{12}$ potentiates the antiplatelet effects of $PGI_{2}$. Methods: We measured the effects of $PGI_{2}$ (0.01–10 μm) on PA of washed human platelets induced by thrombin (0.5 U $mL^{−1}$) in the presence or absence of ARC69931MX $(anti-P2Y_{12}$) or MRS2500 $(anti-P2Y_{1}$). Results: $PGI_{2}$ inhibited PA in the presence of $anti-P2Y_{12}$, but not in the presence of $anti-P2Y_{1}$ or in the absence of inhibitors. In contrast, dibutyryl-cyclicAMP inhibited PA both in the presence and absence of $anti-P2Y_{1}$ or $anti-P2Y_{12}$. $PGI_{2}$ increased platelet cyclicAMP levels only in the absence of thrombin or in the presence of thrombin plus $anti-P2Y_{12}$. Conclusions: $PGI_{2}$ did not inhibit PA induced by thrombin, because its effect on AC was prevented by released ADP interacting with $P2Y_{12}$. $Anti-P2Y_{12}$ drugs, by rescuing AC activity, potentiate the antiplatelet effect of $PGI_{2}$, which may contribute to their antithrombotic effect. |
| Ending Page | 582 |
| Starting Page | 577 |
| ISSN | 2573508X |
| e-ISSN | 15387836 |
| DOI | 10.1111/j.1538-7836.2007.02356.x |
| Journal | Journal of Thrombosis and Haemostasis |
| Issue Number | 3 |
| Volume Number | 5 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2007-02-21 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Thrombosis and Haemostasis Medical Laboratory Technology Adenosine Diphosphate |
| Content Type | Text |
| Resource Type | Article |
