ENDOTHELIN RECEPTORS STIMULATE BOTH PHOSPHOLIPASE-C AND PHOSPHOLIPASE-D ACTIVITIES IN DIFFERENT CELL-LINES
ENDOTHELIN RECEPTORS STIMULATE BOTH PHOSPHOLIPASE-C AND PHOSPHOLIPASE-D ACTIVITIES IN DIFFERENT CELL-LINES
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DOI：
10.1016/0922-4106(93)90166-7
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发表时间：
1993-03-15
期刊：
影响因子：
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通讯作者：
SOKOLOVSKY, M
中科院分区：
文献类型：
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作者：
AMBAR, I;SOKOLOVSKY, M
使用[I-125]ET-1在c6胶质瘤细胞和Rat-1和Swiss 3T3成纤维细胞中进行的内皮素（ET）受体结合试验表明存在两个结合位点，其中一个结合激动剂在pM范围内，另一个在nM范围内。所有三种细胞系在激动剂结合方面表现出相同的药理学特征（ET-1与sarafotoxin-b > ET-3一致），这表明受体为ET(A)型。ET-1与受体结合导致两种磷脂酶，磷脂酶C （PLC）和磷脂酶D （PLD）的激活。内皮素在三种细胞系中对PLC或PLD的激活是通过高亲和力结合位点（nM范围）介导的，细胞外和细胞内Ca2+对其均无显著影响。在两种有效的蛋白激酶C （PKC）抑制剂存在和不存在的情况下，通过ET-1和/或phorbol 12-肉豆蔻酸13-乙酸酯（PMA）激活PLD的测量强烈表明，C6胶质瘤细胞以及大鼠1和Swiss 3T3成纤维细胞中ET受体激活PLD涉及PKC依赖性和PKC非依赖性机制。
Endothelin (ET) receptor-binding assays using [I-125]ET-1 in C6-glioma cells and in Rat-1 and Swiss 3T3 fibroblasts indicated the presence of two binding sites, one of which binds agonists at the pM range and the other at the nM range. All three cell lines exhibited the same pharmacological profile for agonist binding (ET-1 congruent-to sarafotoxin-b > ET-3), which suggests that the receptor is of the ET(A) type. Binding of ET-1 to the receptor resulted in activation of two phospholipases, phospholipase C (PLC) and phospholipase D (PLD). The activation of PLC or PLD by endothelin in the three cell lines was mediated by the high affinity binding site (nM range) and was not significantly affected by either extracellular or intracellular Ca2+. Measurement of PLD activation by ET-1 and/or phorbol 12-myristate 13-acetate (PMA), in the presence and absence of two potent inhibitors of protein kinase C (PKC), strongly suggests that activation of PLD by ET receptor in C6 glioma cells as well as in Rat-1 and Swiss 3T3 fibroblasts involves both PKC-dependent and PKC-independent mechanisms.