血小板P2T(AC) ADP受体的分子克隆:与另一种ADP受体P2Y(1)受体的药理学比较。
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高崎J, Kamohara M，斋藤T，松本M，松本S，大石T，宗贺T，松本H，古义一K
血小板P2T(AC) ADP受体的分子克隆:与另一种ADP受体P2Y(1)受体的药理学比较。
Mol Pharmacol. 2001 9月;60(3):432-9。
- PubMed ID
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11502873 (PubMed视图］
- 摘要
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血小板活化在血栓形成中起着至关重要的作用。ADP诱导的血小板聚集是由两个不同的G蛋白偶联ADP受体介导的，Gq-linked P2Y(1)和Gi-linked P2T(AC)，尚未克隆。分离到编码G蛋白偶联受体的cDNA，称为HORK3。HORK3基因和P2Y(1)基因定位于染色体3q21-q25。转染大鼠胶质瘤细胞亚碱基(C6-15)后，HORK3对2-甲基硫代ADP (2MeSADP) (EC(50) = 0.08 nM)和ADP (EC(50) = 42 nM)有反应，并抑制了forskolin刺激的cAMP积累。在表达P2Y(1)的细胞中，2MeSADP (EC(50) = 1.3 nM)和ADP (EC(50) = 18 nM)也能诱导细胞内钙的动员。这些结果表明HORK3是Gi/o偶联受体，其天然配体为ADP。AR-C69931 MX和2MeSAMP, P2T(AC)拮抗剂选择性地抑制了表达hork3的细胞中2mesadp诱导的腺苷酸环化酶抑制。另一方面，P2Y(1)拮抗剂A3P5PS仅阻断2mesadp诱导的P2Y(1)表达细胞中的钙动员。在人血小板中检测到HORK3 mRNA，其表达水平与P2Y相当(1)。 These observations indicate that HORK3 has the characteristics of the proposed P2T(AC) receptor. We have also determined that [(3)H]2MeSADP binds to cloned HORK3 and P2Y(1). Competition binding experiments revealed a similarity in the rank orders of potency of agonists and the selectivity of antagonists as obtained in the functional assay. These results support the view that P2Y(1) functions as a high-affinity ADP receptor and P2T(AC) as a low-affinity ADP receptor in platelets.