Abstract:
:The effect of selective activation of platelet prostaglandin (PG) E2 receptor subtype EP2 or EP4 on platelet aggregation remains to be determined. In platelets prepared from wild-type mice (WT platelets), high concentrations of PGE2 inhibited platelet aggregation induced by U-46619, a thromboxane receptor agonist. However, there was no significant change in the inhibitory effect of PGE2 on platelets lacking EP2 (EP2-/- platelets) and EP4 (EP4-/- platelets) compared with the inhibitory effect on WT platelets. On the other hand, AE1-259 and AE1-329, agonists for EP2 and EP4, respectively, potently inhibited U-46619 -induced aggregation with respective IC50 values of 590 ± 14 and 100 ± 4.9 nM in WT platelets, while the inhibition was significantly blunted in EP2-/- and EP4-/- platelets. In human platelets, AE1-259 and AE1-329 inhibited U-46619-induced aggregation with respective IC50 values of 640 ± 16 and 2.3 ± 0.3 nM. Notably, the inhibitory potency of AE1-329 in human platelets was much higher than that in murine platelets, while such a difference was not observed in the inhibitory potency of AE1-259. AE1-329 also inhibited adenosine diphosphate-induced platelet aggregation, and the inhibition was almost completely blocked by AE3-208, an EP4 antagonist. In addition, AE1-329 increased intracellular cAMP concentrations in a concentration- and EP4-dependent manner in human platelets. These results indicate that selective activation of EP2 or EP4 can inhibit platelet aggregation and that EP4 agonists are particularly promising as novel anti-platelet agents.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Kuriyama S,Kashiwagi H,Yuhki K,Kojima F,Yamada T,Fujino T,Hara A,Takayama K,Maruyama T,Yoshida A,Narumiya S,Ushikubi Fdoi
10.1160/TH10-01-0043subject
Has Abstractpub_date
2010-10-01 00:00:00pages
796-803issue
4eissn
0340-6245issn
2567-689Xpii
10-01-0043journal_volume
104pub_type
杂志文章abstract::The effects on the haemoglobin level of low dose aspirin and of low intensity oral anticoagulation with warfarin separately and in combination have been established in men aged between 45 and 69 at high risk of ischaemic heart disease. The findings confirm that combined treatment with warfarin and aspirin (WA) leads t...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::The binding properties of purified bovine fibrinogen to bovine aortic endothelial cells have been examined in a tissue culture system. Endothelial cells bound 125I-fibrinogen in a calcium dependent fashion. Removal of calcium by EDTA instantaneously detached most of the cell-associated fibrinogen. Binding of fibrinoge...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-02-18 00:00:00
abstract::Subcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic compli...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-03-04 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1980-12-19 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-12-0898
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH04-03-0182
更新日期:2004-10-01 00:00:00
abstract::Antibodies directed against ADAMTS13 have been detected in the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP). We have previously localized a major antigenic determinant within the spacer domain of ADAMTS13. To identify the amino acid residues of the spacer domain that are involved in bin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH06-03-0135
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-12-28 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-11-0941
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH11-04-0208
更新日期:2011-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2014-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1993-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH03-12-0766
更新日期:2004-03-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:
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pub_type: 杂志文章,多中心研究
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2008-12-01 00:00:00
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journal_title:Thrombosis and haemostasis
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doi:10.1160/TH09-06-0403
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1675399
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2007-11-01 00:00:00