Activation of multiple mechanisms including phospholipase D by endothelin-1 in rat aorta.
Activation of multiple mechanisms including phospholipase D by endothelin-1 in rat aorta.
复制标题
大鼠主动脉中内皮素 1 激活多种机制，包括磷脂酶 D。
DOI：
10.1152/ajpcell.1992.262.4.c941
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Jones,AW
中科院分区：
文献类型：
--
作者：
Liu,Y;Geisbuhler,B;Jones,AW
本研究旨在探讨内皮素-1（ET-1）引起大鼠主动脉收缩的细胞机制，并着重探讨磷脂酶D（PLD）的参与。在无钙溶液中预孵育大鼠主动脉可使收缩减少80%，而地尔硫卓（10 μ M），一种电压操纵性钙通道阻滞剂，仅引起收缩的小幅减少（27%，P <0.05）。在肌-[3 H]肌醇标记的主动脉中，ET-1刺激[3 H]肌醇二磷酸和[3 H]肌醇三磷酸的形成，表明磷脂酶C（PLC）的激活。在用~（32）PO_4、[~ 3 H]肉豆蔻酸或[~（32）P]溶血血小板激活因子标记的主动脉中，暴露于0.5%乙醇后，ET-1刺激磷脂酰乙醇（PEt）的产生，提示ET-1激活PLD。PEt反应不衰减staurosporine（ST，0.1 μ M），蛋白激酶C（PKC）的抑制剂，但被抑制的Ca 2+的去除。ET-1诱导的PEt反应至少与佛波醇12-肉豆蔻酸酯13-乙酸酯（1 μ M）诱导的反应相加。ET-1还刺激6-酮前列腺素F1 α（6-keto-PGF 1 α）释放到组织培养基中。与PEt反应不同，ST可抑制6-keto-PGF 1 α反应。去除Ca ~（2+）可消除该反应。这些结果表明：1）ET-1激活多种细胞机制，包括PLC，PLD和花生四烯酸级联反应; 2）PKC激活可能不是ET-1激活PLD所必需的，但可能在ET-1刺激6-keto-PGF 1 α释放中起重要作用; 3）Ca 2+是ET-1诱导PLD活性和6-keto-PGF 1 α释放的重要因素。
This study investigated the cellular mechanisms underlying the endothelin-1 (ET-1)-induced contraction of rat aorta with focus on the involvement of phospholipase D (PLD). Preincubating rat aorta in Ca(2+)-free solution reduced the contraction by 80%, whereas diltiazem (10 microM), a voltage-operated Ca2+ channel blocker, caused only a small reduction (27%, P less than 0.05) of the contraction. In myo-[3H]inositol-labeled aorta, ET-1 stimulated the formation of [3H]inositol bisphosphate and [3H]inositol trisphosphate, indicating the activation of phospholipase C (PLC). In aorta labeled with 32PO4, [3H] myristic acid or [32P]lyso-platelet-activating factor followed by exposure to ethanol (0.5%), ET-1 stimulated phosphatidylethanol (PEt) production, suggesting that ET-1 activates PLD. The PEt response was not attenuated by staurosporine (ST, 0.1 microM), an inhibitor of protein kinase C (PKC) but was inhibited by removal of Ca2+. The ET-1-induced PEt response was at least additive to that induced by phorbol 12-myristate 13-acetate (1 microM). ET-1 also stimulated the release of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) into the tissue medium. Unlike the PEt responses, the 6-keto-PGF1 alpha response could be inhibited by ST. Removal of Ca2+ abolished the response. These results suggest that 1) ET-1 activates multiple cellular mechanisms including PLC, PLD, and the arachidonate cascade; 2) PKC activation may not be essential for the ET-1 activation of PLD but may play an important role in the ET-1 stimulation of 6-keto-PGF1 alpha release; and 3) Ca2+ is an important factor in the ET-1-induced PLD activity and 6-keto-PGF1 alpha release.