Baurand A, Raboisson P, Freund M, Léon C, Cazenave J P, Bourguignon J J, Gachet C
Laboratoire de Biologie et de Pharmacologie de l'Hémostase et de la Thrombose INSERM U.311, Etablissement Français du Sang-Alsace, 10 rue Spielmann, BP 36, 67065 Cédex, Strasbourg, France.
Eur J Pharmacol. 2001 Feb 2;412(3):213-21. doi: 10.1016/s0014-2999(01)00733-6.
The effects of a potent P2Y1 receptor antagonist, N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179) on adenosine-5'-diphosphate (ADP)-induced platelet aggregation in vitro, ex vivo and on the bleeding time in vivo were determined. In suspensions of washed platelets, MRS2179 inhibited ADP-induced platelet shape change, aggregation and Ca2+ rise but had no effect on ADP-induced inhibition of adenylyl cyclase. Binding studies using the new radioligand [33P]MRS2179 showed that washed human platelets displayed 134+/-8 binding sites per platelet with an affinity (Kd) of 109+/-18 nM. Finally, intravenous injection of MRS2179 resulted in inhibition of rat platelet aggregation in response to ADP and prolonged the bleeding time, in rats or mice, as compared to controls. These results suggest this potent P2Y1 receptor antagonist to be a promising tool to evaluate the in vivo effects of pharmacologically targeting the P2Y1 receptor with a view to antithrombotic therapy.
研究了强效P2Y1受体拮抗剂N6-甲基-2'-脱氧腺苷-3',5'-双磷酸酯（MRS2179）对体外、离体二磷酸腺苷（ADP）诱导的血小板聚集以及体内出血时间的影响。在洗涤过的血小板悬液中，MRS2179抑制ADP诱导的血小板形状改变、聚集和钙离子升高，但对ADP诱导的腺苷酸环化酶抑制作用无影响。使用新型放射性配体[33P]MRS2179进行的结合研究表明，洗涤过的人血小板每个血小板显示134±8个结合位点，亲和力（Kd）为109±18 nM。最后，静脉注射MRS2179可抑制大鼠对ADP的血小板聚集反应，并与对照组相比延长大鼠或小鼠的出血时间。这些结果表明，这种强效P2Y1受体拮抗剂有望成为一种评估以抗血栓治疗为目的对P2Y1受体进行药理学靶向体内效应的工具。
