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Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
The P2Y1 receptor mediates ADP-induced p38 kinase-activating factor generation in human platelets
C Dangelmaier1, J Jin, J L Daniel
1Department of Pharmacology, Temple University Medical School, Philadelphia, PA, USA.
European Journal of Biochemistry
|April 12, 2000
Summary
Adenosine diphosphate (ADP) activates p38 mitogen-activated protein (MAP) kinase in human platelets via a thromboxane A2-independent pathway. The P2Y1 receptor mediates ADP-induced p38 MAP kinase activation, highlighting a novel signaling mechanism.
Area of Science:
- Biochemistry
- Molecular Biology
- Platelet Physiology
Background:
- Platelet activation is crucial for hemostasis and thrombosis.
- Mitogen-activated protein (MAP) kinases, including p38 MAP kinase, play significant roles in platelet function.
- Adenosine diphosphate (ADP) is a key agonist in platelet activation, but its precise signaling pathways leading to p38 MAP kinase activation remain incompletely understood.
Purpose of the Study:
- To elucidate the signaling pathway by which ADP activates p38 MAP kinase in human platelets.
- To determine the role of thromboxane A2 and other cyclooxygenase products in ADP-mediated p38 MAP kinase activation.
- To identify the specific ADP receptor(s) involved in this signaling cascade.
Main Methods:
- Human platelets were treated with various agonists and antagonists.
- p38 MAP kinase activation was assessed using Western blotting or kinase assays.
- Specific receptor antagonists (e.g., SQ29548, AR-C66096, adenosine-2'-phosphate-5'-phosphate) and inhibitors (e.g., furegrelate, indomethacin) were employed.
Main Results:
- U46619 (thromboxane A2 mimetic) activated p38 MAP kinase in aspirin-treated platelets.
- ADP activated p38 MAP kinase in non-aspirinated platelets in a time- and concentration-dependent manner.
- Neither thromboxane A2 pathway inhibitors nor P2TAC/P2X receptor antagonists blocked ADP-induced p38 MAP kinase activation.
- A P2Y1 receptor antagonist significantly inhibited ADP-induced p38 MAP kinase activation.
Conclusions:
- ADP activates p38 MAP kinase in human platelets through a pathway independent of thromboxane A2.
- The P2Y1 receptor is the primary mediator of ADP-induced p38 MAP kinase activation.
- These findings reveal a novel ADP-P2Y1 receptor-mediated signaling pathway for p38 MAP kinase activation in platelets.
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