摘要
目的 探讨酪氨酸激酶在Ca2 +池操纵性Ca2 +内流中的作用。方法 记录大鼠胸主动脉环收缩反应。结果 ①不同剂量酪氨酸激酶抑制剂 genistein (1～ 10 0 μmol·L-1)和tyrphostin 2 5 (Tyr 2 5 ,1～ 30 μmol·L-1)均以浓度依赖性抑制cyclopiazonicacid (CPA)引起的平滑肌收缩平台期。Tyr 2 5的最大作用浓度为 10 μmol·L-1,抑制率为 42 %±11%。② 10 μmol·L-1Tyr 2 5和 1μmol·L-1nifedipine(Nif)对CPA引起电压依赖性Ca2 +通道 (VDCC)开放过程的抑制作用存在部分交叉。③ 1μmol·L-1Nif预处理阻断VDCC作用后 ,10 μmol·L-1Tyr 2 5只能部分阻断CPA引起的Ca2 +池操纵性Ca2 +通道 (SOCC)开放过程 ,再加入 6 0 μmol·L-1SK&F96 36 5可完全阻断SOCC的开放过程。结论 CPA引起平滑肌的收缩过程中 。
AIM To study the relationship between store operated Ca 2+ influx and tyrosine kinase inhibitor in rat vascular smooth muscle. METHOD The tension of rat aortic ring was measured. RESULTS ①Tyrosine kinase inhibitor genistein (1～100 μmol·L -1 )and tyrphostin 25 (Tyr 25, 1～30 μmol·L -1 ) produced a concentration dependent inhibitory effect on 10 μmol·L -1 CPA induced contractile response. Inhibitory rate of 100 μmol·L -1 genistein was 92%±8%. The maximal inhibitory effect (42%±11% ) of Tyr 25 was reached in the concentration of 10 μmol·L -1 . ②There was an overlap effects on VDCC Tyr 25 (10 μmol·L -1 ) and Nif(1 μmol·L -1 ). ③ Pre incubation of 1 μmol·L -1 Nif obviously inhibited 10 μmol·L -1 CPA induced contractile response. In this case, addition of 10 μmol·L -1 Tyr 25 further decreased the contractile response due to the Ca 2+ entry through SOCC,and subsequently addition of 60 μmol·L -1 SK&F96365 completely depressed this contracile response. CONCLUTION Tyrosine kinase participates in the signal tansduction in the process of SOCC and VDCC opening which mediated store operated Ca 2+ influx.
出处
《中国药理学通报》
CSCD
北大核心
2000年第4期409-412,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助课题! (No 39770 85 8)
美国中华医学基金资助课题
关键词
酪氨酸激酶抑制剂
GENISTEIN
主动脉血管环收缩
store operated Ca^(2+) influx
Ca^(2+) channels
cyclopiazonic acid
vascular smooth muscle
tyrosine kinase inhibitor
SK&F96365
