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ADP receptors and clinical bleeding disorders
1Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ospedale Maggiore, University of Milano, Milano, Italy. marco.cattaneo@unimi.it
Arteriosclerosis, Thrombosis, and Vascular Biology
|October 16, 1999
Summary
Adenosine diphosphate (ADP) triggers platelet aggregation through three purinergic receptors. Understanding these receptors clarifies ADP
Area of Science:
- Biochemistry
- Hematology
- Pharmacology
Background:
- Adenosine diphosphate (ADP) is a critical mediator in hemostasis and thrombosis.
- The molecular mechanisms underlying ADP-induced platelet activation remain incompletely understood.
- Platelet aggregation is a complex process involving multiple signaling pathways.
Purpose of the Study:
- To propose a model detailing the roles of three distinct purinergic receptors in ADP-induced platelet aggregation.
- To elucidate the specific functions of P2X(1) and P2Y(1) receptors in calcium signaling during platelet activation.
- To identify the putative receptor targeted by antiplatelet drugs like ticlopidine and clopidogrel.
Main Methods:
- Review of existing literature on purinergic signaling and platelet function.
- Analysis of the known roles of P2X(1) and P2Y(1) receptors in calcium mobilization.
- Hypothesizing the existence and function of an unidentified G(alphai2)-coupled P2Y receptor.
Main Results:
- A model is proposed involving three purinergic receptors: P2X(1), P2Y(1), and an unidentified P2Y receptor.
- P2X(1) facilitates rapid cytosolic calcium influx.
- P2Y(1) mobilizes internal calcium stores, initiating aggregation, while the third receptor is crucial for full aggregation response.
Conclusions:
- The three-receptor model provides a framework for understanding ADP-mediated platelet aggregation.
- The unidentified P2Y receptor is likely the target of ticlopidine and clopidogrel.
- Defects in this receptor may underlie bleeding disorders with impaired platelet responses to ADP.