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Purinoceptor-evoked calcium signalling in human platelets
S O Sage1, A B MacKenzie, S Jenner
1The Physiological Laboratory, University of Cambridge, UK. sos10@cus.cam.ac.uk
Prostaglandins, Leukotrienes, and Essential Fatty Acids
|January 16, 1998
Summary
Adenosine diphosphate (ADP) triggers calcium (Ca2+) spikes in platelets by releasing stored Ca2+ and promoting Ca2+ entry through distinct pathways, including a P2X1 purinoceptor-activated channel.
Area of Science:
- Cellular biology
- Biochemistry
- Physiology
Background:
- Adenosine diphosphate (ADP) is a key signaling molecule in platelet activation.
- ADP stimulates an increase in intracellular calcium (Ca2+) concentration, crucial for platelet function.
- Platelet Ca2+ response involves both release from internal stores and influx from extracellular sources.
Purpose of the Study:
- To elucidate the mechanisms by which ADP modulates cytosolic Ca2+ concentration in platelets.
- To differentiate the signaling pathways activated by ADP leading to Ca2+ release and Ca2+ entry.
- To identify the purinergic receptors involved in ADP-mediated Ca2+ signaling.
Main Methods:
- Single-cell calcium imaging techniques.
- Pharmacological characterization of ion channels and receptors.
- Investigation of inositol trisphosphate generation and protein tyrosine phosphorylation.
Main Results:
- ADP induces oscillatory spikes in cytosolic Ca2+.
- Ca2+ release is mediated by inositol 1,4,5-trisphosphate, leading to store-operated Ca2+ entry involving protein tyrosine phosphorylation.
- A distinct P2X1 purinoceptor mediates rapid Ca2+ and Na+ entry, activated by ATP and diadenosine tetraphosphate.
Conclusions:
- ADP activates multiple, distinct Ca2+ signaling pathways in platelets.
- The P2X1 purinoceptor plays a specific role in rapid cation influx, separate from store-operated Ca2+ entry.
- Understanding these pathways is critical for comprehending platelet aggregation and thrombosis.