Regulation of tyrosine hydroxylase gene expression by muscarinic agonists in rat adrenal medulla.
Regulation of tyrosine hydroxylase gene expression by muscarinic agonists in rat adrenal medulla.
复制标题
毒蕈碱激动剂对大鼠肾上腺髓质酪氨酸羟化酶基因表达的调节。
DOI：
10.1046/j.1471-4159.1999.0730153.x
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发表时间：
1999
影响因子：
4.7
通讯作者：
Tank,AW
中科院分区：
文献类型：
--
作者：
Piech-Dumas,KM;Sterling,CR;Tank,AW
摘要：肾上腺髓质中酪氨酸羟化酶（TH）基因的表达受到多种刺激通过突触机制的调节。介导这种跨突触反应的肾上腺嗜铬细胞受体仍不清楚。在本报告中，我们证明毒蕈碱乙酰胆碱受体激动剂氨甲酰胆碱可刺激受神经支配和去神经支配的肾上腺中的 TH 基因转录率。因此，这种毒蕈碱反应不依赖于突触影响，表明激动剂占据肾上腺嗜铬细胞毒蕈碱受体足以激活刺激TH基因的细胞内信号传导途径。当以 3 小时为间隔重复注射氨甲酰甲胆碱（四次注射，间隔 1 小时）时，TH mRNA 水平在初次注射药物后 6 小时和 12 小时时增加了两到三倍。令人惊讶的是，TH mRNA 的这种诱导不会导致 TH 活性或 TH 蛋白水平的增加。这些结果与以下假设一致：转录和转录后机制必须受到调节才能诱导 TH 蛋白，并且毒蕈碱激动剂仅激活这些机制的一部分。
Abstract:Tyrosine hydroxylase (TH) gene expression in the adrenal medulla is regulated by numerous stimuli via transsynaptic mechanisms. The adrenal chromaffin cell receptors that mediate this transsynaptic response remain unidentified. In this report we demonstrate that the muscarinic acetylcholine receptor agonist bethanechol stimulates the TH gene transcription rate in both innervated and denervated adrenal glands. Hence, this muscarinic response is not dependent on transsynaptic influences, suggesting that agonist occupation of adrenal chromaffin cell muscarinic receptors is sufficient to activate intracellular signaling pathways that stimulate the TH gene. When bethanechol is administered repeatedly over a 3‐h interval (four injections spaced 1 h apart), TH mRNA levels are increased two‐ to threefold at 6 and 12 h after the initial injection of drug. It is surprising that this induction of TH mRNA does not lead to increases in TH activity or TH protein level. These results are consistent with the hypothesis that both transcriptional and posttranscriptional mechanisms must be regulated to induce TH protein and that muscarinic agonists activate only a subset of these mechanisms.