Both the ADP receptors P2Y1 and P2Y12, play a role in controlling shape change in human platelets
Both the ADP receptors P2Y1 and P2Y12, play a role in controlling shape change in human platelets
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DOI：
10.1080/0953710021000062914
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Mikhailidis, DP
中科院分区：
文献类型：
--
作者：
Jagroop, IA;Burnstock, G;Mikhailidis, DP
两种类型的ADP受体P2Y（1）和P2Y（12）参与血小板聚集。P2X（1）受体也存在，但其在血小板功能方面的作用尚未确定。本研究的目的是确定ADP受体P2Y（1）、P2Y（12）和P2X（1）是否在控制人血小板中血小板形状改变（PSC）中起作用。PSC是血小板聚集前的早期活化阶段，采用高分辨率通道仪，通过测量血小板体积中位数（MPV）来评估PSC。P2Y（1）受体拮抗剂MRS 2179（1.06 - 10.25 μ mol/l）阻断ADP诱导的PSC（100%）。中位IC 50为3.16 mumol/l。MRS 2179对ADP +5-羟色胺（5HT）诱导的PSC也有显著的抑制作用（P = 0.01）。P2Y（12）受体拮抗剂AR-C69931MX显著抑制ADP诱导的PSC（10 s，P = 0.009; 15 s，P = 0.001; 30 s，P = 0.015）。P2X（1）受体拮抗剂TNP-ATP对ADP或ADP +5HT诱导的PSC无明显影响。我们的结论是，由于channelyzer技术的高分辨率和重复性，可以推导出P2Y（1）受体阻断剂的IC 50。除了P2Y（1）嘌呤受体外，P2Y（12）受体似乎也参与ADP诱导的PSC，因为AR-C69931MX显著抑制了这一过程。channelyzer技术可能比光学聚集测定法更可靠地评估PSC。
Two types of ADP receptors, P2Y(1) and P2Y(12) are involved in platelet aggregation. The P2X(1) receptor is also present but its role, in terms of platelet function, is not yet defined. The aim of this study was to establish if the ADP receptors, P2Y(1), P2Y(12) and P2X(1) play a role in controlling platelet shape change (PSC) in human platelets. PSC is an early phase of platelet activation that precedes aggregation.Using a high-resolution channelyzer, PSC was assessed by measuring the median platelet volume (MPV). The P2Y(1) receptor antagonist MRS 2179 (1.06-10.25 mumol/l) blocked ADP-induced PSC (by 100%). The median IC50 was 3.16 mumol/l. MRS 2179 also significantly (P = 0.01) inhibited PSC induced by the combination of ADP + serotonin (5HT). The P2Y(12) receptor antagonist AR-C69931MX significantly inhibited (at 10s, P = 0.009; 15 s, P = 0.001 and 30 s, P = 0.015) ADP-induced PSC. The P2X(1) receptor antagonist TNP-ATP had no significant effect on ADP- or ADP + 5HT-induced PSC.We conclude that the IC50 of a P2Y(1)-blocker can be derived because of the high-resolution and reproducibility of the channelyzer technique. In addition to the P2Y(1) purinoceptor, the P2Y(12) receptor appears to be involved in ADP-induced PSC since this process was significantly inhibited by AR-C69931MX. The channelyzer technique may be more reliable than optical aggregometry to assess PSC.