DOI: 10.1046/j.1365-2141.2000.02208.x. The central role of the P<sub><i>2T</i></sub> receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity

The central role of the P2T receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity

10.1046/j.1365-2141.2000.02208.x

Crossref journal-article

Wiley

British Journal of Haematology (311)

Abstract

Adenosine diphosphate (ADP) is an important platelet agonist and ADP released from platelet dense granules amplifies responses to other agonists. There are three known subtypes of ADP receptor on platelets: P2X1, P2Y1 and P2T receptors. Sustained ADP‐induced aggregation requires co‐activation of P2Y1 and P2T receptors. AR‐C69931MX, a selective P2T receptor antagonist and novel antithrombotic agent, was studied to characterize further the function of the P2T receptor. The roles of the P2Y1 receptor and thromboxane A2 were assessed using the selective P2Y1 antagonist A2P5P and aspirin respectively. Aggregation was measured by whole blood single‐platelet counting and platelet‐rich plasma turbidimetry, using hirudin anticoagulation. Dense granule release was estimated using [14C]‐5‐hydroxytryptamine (HT)‐labelled platelets. Ca2+ mobilization, P‐selectin expression, Annexin V binding and microparticle formation were determined by flow cytometry. P2T receptor activation amplified ADP‐induced aggregation initiated by the P2Y1 receptor, as well as amplifying aggregation, secretion and procoagulant responses induced by other agonists, including U46619, thrombin receptor‐activating peptide (TRAP) and collagen, independent of thromboxane A2 synthesis, which played a more peripheral role. P2T receptor activation sustained elevated cytosolic Ca2+ induced by other pathways. These studies indicate that the P2T receptor plays a central role in amplifying platelet responses and demonstrate the clinical potential of P2T receptor antagonists.

Bibliography

Storey, R. F., Sanderson, H. M., White, A. E., May, J. A., Cameron, K. E., & Heptinstall, S. (2000). The central role of the P2T receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. British Journal of Haematology, 110(4), 925â934. Portico.

Authors 6

Robert F. Storey (first)
Heather M. Sanderson (additional)
Ann E. White (additional)
Jane A. May (additional)
Kathryn E. Cameron (additional)
Stan Heptinstall (additional)

References 44 Referenced 232

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Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 1:28 a.m.)
Deposited	1 year, 10 months ago (Oct. 29, 2023, 1:30 p.m.)
Indexed	1 day, 4 hours ago (Aug. 29, 2025, 5:48 a.m.)
Issued	24 years, 11 months ago (Sept. 1, 2000)
Published	24 years, 11 months ago (Sept. 1, 2000)
Published Online	23 years, 8 months ago (Dec. 24, 2001)
Published Print	24 years, 11 months ago (Sept. 1, 2000)

Funders 0

None

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