D1 dopamine receptor agonists mediate activation of p38 mitogen-activated protein kinase and c-Jun amino-terminal kinase by a protein kinase A-dependent mechanism in SK-N-MC human neuroblastoma cells.
D1 dopamine receptor agonists mediate activation of p38 mitogen-activated protein kinase and c-Jun amino-terminal kinase by a protein kinase A-dependent mechanism in SK-N-MC human neuroblastoma cells.
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DOI：
10.1124/mol.54.3.453
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发表时间：
1998-09
影响因子：
3.6
通讯作者：
Xuechu Zhen;K. Uryu;Hoau Yan Wang;E. Friedman
中科院分区：
文献类型：
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作者：
Xuechu Zhen;K. Uryu;Hoau Yan Wang;E. Friedman
我们研究了多巴胺D1受体刺激对SK-N-MC人神经母细胞瘤细胞中丝裂原活化蛋白激酶（MAPK）活化的影响。我们发现，D1多巴胺受体激动剂SKF 38393诱导p38 MAPK和c-Jun氨基末端激酶（JNK）类似的时间和剂量相关的激活，而细胞外信号调节激酶活性不受D1多巴胺受体刺激。用100 μ M SKF 38393孵育15分钟后，观察到p38 MAPK和JNK的最大刺激。相比之下，10 μ M的喹吡罗，一种D2多巴胺受体激动剂，不激活p38 MAPK或JNK。用10 μ M SCH 23390（一种D1多巴胺受体拮抗剂）处理细胞，可显著抑制SKF 38393对这两种激酶的激活。这些结果表明，在SK-N-MC神经母细胞瘤细胞中，p38 MAPK和JNK信号通路的激活由多巴胺D1受体介导。此外，二丁酰-cAMP模拟SKF 38393介导的p38 MAPK和JNK刺激。1 μ M H-89或10 μ M腺苷3 '，5'-环硫代磷酸（Rp-异构体，三乙基铵盐）抑制蛋白激酶A可显著减弱p38 MAPK和JNK的激活。相反，选择性蛋白激酶C抑制剂calphostin C不能阻断D1多巴胺受体刺激的p38 MAPK和JNK的激活。这些结果表明，第一次，GS-偶联D1多巴胺受体激活p38 MAPK和JNK信号通路的蛋白激酶A依赖的机制。
We investigated the effects of D1 dopamine receptor stimulation on the activation of mitogen-activated protein kinases (MAPKs) in SK-N-MC human neuroblastoma cells. We found that the D1 dopamine receptor agonist SKF38393 induced similar time- and dose-related activation of p38 MAPK and c-Jun amino-terminal kinase (JNK), whereas extracellular signal-regulated kinase activity was not affected by D1 dopamine receptor stimulation. Maximal stimulation of p38 MAPK and JNK was observed after a 15-min incubation with 100 microM SKF38393. In contrast, 10 microM quinpirole, a D2 dopamine receptor agonist, did not activate p38 MAPK or JNK. Treatment of cells with 10 muM SCH23390, a D1 dopamine receptor antagonist, significantly inhibited the activation of both kinases by SKF38393. These results indicate that activation of the p38 MAPK and JNK signaling pathways is mediated by dopamine D1 receptors in SK-N-MC neuroblastoma cells. Furthermore, dibutyryl-cAMP mimicked SKF38393-mediated stimulation of p38 MAPK and JNK. Inhibition of protein kinase A by 1 microM H-89 or 10 microM adenosine 3', 5'-cyclic monophosphothioate (Rp-isomer, triethylammonium salt) markedly attenuated the activation of p38 MAPK and JNK. Conversely, the selective protein kinase C inhibitor calphostin C did not block D1 dopamine receptor-stimulated activation of p38 MAPK and JNK. These results demonstrate, for the first time, that the Gs-coupled D1 dopamine receptor activates the p38 MAPK and JNK signaling pathways by a protein kinase A-dependent mechanism.