ML-7 and W-7 facilitate thromboxane A2-mediated Ca2+ mobilization in rabbit platelets.

ML-7 and W-7 facilitate thromboxane A2-mediated Ca2+ mobilization in rabbit platelets.
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ML-7 和 W-7 促进兔血小板中血栓素 A2 介导的 Ca2 动员。

DOI:
10.1016/0014-2999(95)00788-1
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发表时间:
1996
影响因子:
5
通讯作者:
Y. Ohizumi
Y. Ohizumi
中科院分区:
医学2区
文献类型:
--
作者:
S. Ohkubo;N. Nakahata;Y. Ohizumi

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本文观察了肌球蛋白轻链激酶抑制剂1-(5-碘萘-1-磺酰基)-1H-六氢-1,4-二氮杂卓(ML-7)和钙调素拮抗剂N-(6-氨基己基)-5-氯-1-萘磺酰胺(W-7)对兔血小板血栓素A2受体介导的信号转导的影响。尽管ML-7和W-7具有已知的抑制作用,但10-30 μM的ML-7和W-7可轻微增强血栓烷A2受体激动剂9,11-双脱氧-9 α,11 α-环氧甲氧前列腺素F2α(U46619)诱导的聚集。ML-7和W-7浓度依赖性地增强U46619诱导的磷酸肌醇水解和增加内部游离Ca 2+浓度的存在或不存在外部Ca 2+。虽然ML-7和W-7抑制基础GT3活性,但它们以浓度依赖性方式增强U46619诱导的GT3活化。本研究结果表明,ML-7和W-7增强血栓烷A2受体介导的信号转导在受体/G蛋白偶联,导致磷酸肌醇水解和Ca 2+动员的增强,独立于肌球蛋白轻链激酶或钙调蛋白的抑制。
The effects of 1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1, 4-diazepine (ML-7), a myosin light chain kinase inhibitor, and (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, on thromboxane A2receptor-mediated signal transduction were examined in rabbit washed platelets. ML-7 and W-7 at 10–30 μM slightly potentiated the aggregation induced by a thromboxane A2receptor agonist, 9, 11-dideoxy-9α, 11 α-epoxymethanoprostaglandin F2α (U46619), in spite of their known inhibitory actions. ML-7 and W-7 concentration-dependently enhanced U46619-induced phosphoinositide hydrolysis and the increase in internal free Ca2+concentration in the presence or absence of external Ca2+. While ML-7 and W-7 inhibited basal GTPase activity, they augmented U46619-induced activation of GTPase in a concentration-dependent manner. The present results suggest that ML-7 and W-7 enhance thromboxane A2receptor-mediated signal transduction at the receptor/G protein coupling, leading to the enhancement of phosphoinositide hydrolysis and Ca2+mobilization, independently of the inhibition of myosin light chain kinase or calmodulin.
Ca2 和肌球蛋白轻链激酶参与胶原诱导的血小板活化。
DOI: 10.1016/s0309-1651(06)80168-2
发表时间: 1992
期刊: Cell biology international reports
影响因子: --
作者:
Lokeshwar,VB;Bourguignon,LY
通讯作者: Bourguignon,LY
DOI: 10.1016/s0021-9258(17)42774-8
发表时间: 1984-08
期刊: The Journal of biological chemistry
影响因子: --
作者:
J. Daniel;I. Molish;M. Rigmaiden;G. Stewart
通讯作者: J. Daniel;I. Molish;M. Rigmaiden;G. Stewart
钙调蛋白拮抗剂(司特拉嗪)对激动剂诱导的钙动员和血小板活化的影响。
DOI: 10.1016/0006-291x(87)90942-9
发表时间: 1987
影响因子: 3.1
作者:
Rao,GH
通讯作者: Rao,GH