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The ATP-Gated P2X1 Ion Channel Acts as a Positive Regulator of Platelet Responses to Collagen

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2001: 86/5 (Nov) pp.1136-1342
Pages: 1264-1271

The ATP-Gated P2X1 Ion Channel Acts as a Positive Regulator of Platelet Responses to Collagen

Cecile Oury(1), *, Emese Toth-Zsamboki(1), *, Chantal Thys(1), Jan Tytgat(2), Jos Vermylen(1), Marc F. Hoylaerts(1)
(1)Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium, (2)Laboratory of Toxicology, University of Leuven, Belgium

Summary

ATP is a potent agonist of the P2X1 ion channel, mediating a rapid, quickly desensitized influx of Ca2+. In hirudinized PRP, containing apyrase, the two stable selective P2X1 agonists, α,β-methylene ATP, and L-β,γ-methylene ATP induced extracellular Ca2+-dependent fast and reversible platelet shape change, leading to desensitization of the P2X1 ion channel. Preincubation with HPLC-purified ADP potently antagonized the subsequent α,β-methylene ATP- and L-β,γ-methylene ATP-evoked platelet shape change. Accordingly, upon heterologous expression of P2X1 in Xenopus oocytes, HPLC-purified ADP acted as an antagonist of the ATP-induced current, but was inactive itself. Since ATP and ADP are co-released from dense granules during platelet activation, we investigated whether the P2X1 ion channel is involved in the response of platelets to collagen. We found that platelet shape change and aggregation induced by low concentrations of collagen were strongly inhibited after selective desensitization of P2X1 with its agonists or by pretreating the platelets with a low concentration of ADP (0.5 µM), that antagonizes the P2X1 channel without desensitizing the P2Y1 receptor. Our data suggest that, during collagen-initiated platelet activation, the early secretion of ATP results in the activation of the P2X1 ion channel, which plays a role as a positive regulator of further platelet responses.