Kawasaki Tomihisa, Taniguchi Masatoshi, Moritani Yumiko, Hayashi Kazumi, Saito Tetsu, Takasaki Jun, Nagai Koji, Inagaki Osamu, Shikama Hisataka
Cardiovascular Diseases Research, Pharmacology Laboratories, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Thromb Haemost. 2003 Sep;90(3):406-13. doi: 10.1160/TH03-02-0115.
We examined the antithrombotic and thrombolytic effects of the G(q/11) inhibitor YM-254890 in an electrically-induced carotid artery thrombosis model in rats. YM-254890 dose-dependently inhibited ex vivo ADP-induced platelet aggregation after i.v. bolus injection. In the thrombosis study, YM-254890 dosedependently prolonged time to occlusion at doses of 3 and 10 g/kg i.v. and decreased occlusion rate at 10 g/kg i.v. In the thrombolysis study, YM-254890 at 30 micro g/kg i.v. shortened the time to reperfusion and prevented reocclusion after thrombolysis with a modified tissue-type plasminogen activator. YM-254890, at 10 micro g/kg and more, significantly improved carotid patency status after thrombolysis. However, at 30 micro g/kg and more, YM-254890 decreased systemic blood pressure. These results suggest that YM-254890 may be effective for treating G(q)-mediated diseases, and that YM-254890 is a useful tool for investigating the biological roles of G(q/11).
我们在大鼠电诱导颈动脉血栓形成模型中研究了G(q/11)抑制剂YM-254890的抗血栓形成和溶栓作用。静脉推注后，YM-254890剂量依赖性地抑制体外ADP诱导的血小板聚集。在血栓形成研究中，静脉注射3和10μg/kg剂量的YM-254890可剂量依赖性地延长闭塞时间，静脉注射10μg/kg剂量可降低闭塞率。在溶栓研究中，静脉注射30μg/kg剂量的YM-254890可缩短再灌注时间，并在用改良组织型纤溶酶原激活剂溶栓后防止再闭塞。静脉注射10μg/kg及以上剂量的YM-254890可显著改善溶栓后的颈动脉通畅状态。然而，静脉注射30μg/kg及以上剂量的YM-254890会降低全身血压。这些结果表明，YM-254890可能对治疗G(q)介导的疾病有效，并且YM-254890是研究G(q/11)生物学作用的有用工具。
