Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways
Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways
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DOI：
10.1152/ajpheart.1997.272.1.h130
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发表时间：
1997-01-01
影响因子：
4.8
通讯作者：
Brunton, LL
中科院分区：
文献类型：
--
作者：
HilalDandan, R;Ramirez, MT;Brunton, LL
Pie 表征了内皮素 (ET) 与培养的新生大鼠心室肌细胞的相互作用。结合研究表明 ET(A) 受体为单一群体 [53,000 个位点/细胞，ET-1 的表观解离常数 (K-d) 约为 0.07 nM]。使用 35 个循环的逆转录酶-聚合酶链式反应对 ET 受体的 mRNA 水平进行分析，表明仅存在 ET(A) 受体信息。对 ET-1 以及多种同源物和拮抗剂的研究表明，ET(A) 受体既能刺激磷酸肌醇周转，又能抑制腺苷酸环化酶。在用与荧光素酶报告基因连接的心房钠尿因子 (ANF) 启动子转染的肌细胞中，ET-1 通过 ET(A) 受体刺激荧光素酶表达。这些数据表明 ET(A) 受体是新生儿心室肌细胞上的唯一受体，并且该受体与磷酸肌醇水解和腺苷酸环化酶偶联。 ET-1 还可诱导丝裂原激活蛋白激酶 (MAPK) 活性增加三倍，这种作用对百日咳毒素 (PTx) 不敏感。相比之下，用PTx处理细胞会部分抑制ET刺激的ANF荧光素酶表达，这表明PTx敏感(G(i))和PTx不敏感(G(q))途径介导ET-1对新生儿肌细胞中ANF基因表达的影响，并且ANF表达的激素调节除了激活MAPK之外还可能利用该途径。
Pie have characterized the interaction of endothelin (ET) with cultured neonatal rat ventricular myocytes. Binding studies indicate a single population of ET(A) receptors [53,000 sites/cell, apparent dissociation constant (K-d) for ET-1 approximate to 0.07 nM]. Analysis of mRNA levels for ET receptors using 35 cycles of reverse transcriptase-polymerase chain reaction demonstrates the presence of only ET(A)-receptor message. Studies with ET-1 and a variety of congeners and antagonists indicate that ET(A) receptors couple to both the stimulation of phosphoinositide turnover and the inhibition of adenylyl cyclase. In myocytes transfected with an atrial natriuretic factor (ANF) promoter linked to a luciferase reporter gene, ET-1 stimulates luciferase expression through an ET(A) receptor. These data indicate that the ET(A) receptor is the exclusive receptor on neonatal ventricular myocytes and that this receptor couples to both phosphoinositide hydrolysis and adenylyl cyclase. ET-1 also induces a threefold increase in mitogen-activated protein kinase (MAPK) activity, an effect that is not sensitive to pertussis toxin (PTx). By contrast, ET-stimulated ANF-luciferase expression is partially inhibited by treatment of cells with PTx, suggesting that both PTx-sensitive (G(i)) and PTx-insensitive (G(q)) pathways mediate the effects of ET-1 on ANF gene expression in neonatal myocytes and that hormonal regulation of ANF expression may utilize pathways in addition to the activation of MAPK.