Corticotropin induces the expression of TREK-1 mRNA and K+ current in adrenocortical cells.
Corticotropin induces the expression of TREK-1 mRNA and K+ current in adrenocortical cells.
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DOI：
10.1124/mol.64.1.132
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发表时间：
2003-07
影响因子：
3.6
通讯作者：
J. A. Enyeart;S. Danthi;J. J. Enyeart-J.
中科院分区：
文献类型：
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作者：
J. A. Enyeart;S. Danthi;J. J. Enyeart-J.
牛肾上腺束状带（AZF）细胞表达一个双孔/四跨膜段btrek - 1k +通道，该通道设置静息电位，并将激素信号偶联到去极化依赖的Ca2+进入和皮质醇分泌。结果发现，促肾上腺皮质激素（1-2000 pM）可提高培养AZF细胞bTREK-1 mRNA的表达和膜电流。Forskolin和8-pcpt-cAMP模拟促肾上腺皮质激素诱导bTREK-1 mRNA，但血管紧张素II （AII）无效。促肾上腺皮质激素对bTREK-1 mRNA的诱导被a激酶拮抗剂H-89部分阻断。8-（4-氯苯基硫）-2- o-甲基腺苷-3'-5'-环单磷酸，一种激活cAMP调节的鸟嘌呤核苷酸交换因子（Epac）的cAMP类似物，未能增加bTREK-1 mRNA。促肾上腺皮质激素刺激的bTREK-1 mRNA升高被蛋白质合成或基因转录抑制剂消除。bTREK-1电流在添加血清的培养基中24小时后消失，但在促肾上腺皮质激素的存在下，bTREK-1的表达维持至少48小时。在AZF细胞中，bTREK-1 mRNA和离子电流的增强与促肾上腺皮质激素诱导的Kv1.4电压门控K+电流和相关mRNA的下调形成对比。这些结果表明，促肾上腺皮质激素通过camp依赖机制在翻译前水平快速有效地诱导AZF细胞中bTREK-1的表达，该机制部分依赖于a激酶，但不依赖于Epac和Ca2+。他们进一步指出，在长期应激或疾病期间，促肾上腺皮质激素对AZF细胞的长时间刺激可能会导致编码离子通道的基因表达发生显著变化，从而重塑这些细胞的电学特性，以增强或限制皮质醇分泌。
Bovine adrenal zona fasciculata (AZF) cells express a two-pore/four-transmembrane segment bTREK-1 K+ channel that sets the resting potential and couples hormonal signals to depolarization-dependent Ca2+ entry and cortisol secretion. It was discovered that corticotropin (1-2000 pM) enhances the expression of bTREK-1 mRNA and membrane current in cultured AZF cells. Forskolin and 8-pcpt-cAMP mimicked corticotropin induction of bTREK-1 mRNA, but angiotensin II (AII) was ineffective. The induction of bTREK-1 mRNA by corticotropin was partially blocked by the A-kinase antagonist H-89. 8-(4-Chloro-phenylthio)-2-O-methyladenosine-3'-5'-cyclic monophosphate, a cAMP analog that activates cAMP-regulated guanine nucleotide exchange factors (Epac), failed to increase bTREK-1 mRNA. Corticotropin-stimulated increases in bTREK-1 mRNA were eliminated by inhibitors of protein synthesis or gene transcription. bTREK-1 current disappeared after 24 h in serum-supplemented medium, but in the presence of corticotropin, bTREK-1 expression was maintained for at least 48 h. The enhancement of bTREK-1 mRNA and ionic current contrasts with the corticotropin-induced down-regulation of the Kv1.4 voltage-gated K+ current and associated mRNA in AZF cells. These results demonstrate that corticotropin rapidly and potently induces the expression of bTREK-1 in AZF cells at the pretranslational level by a cAMP-dependent mechanism that is partially dependent on A-kinase but independent of Epac and Ca2+. They further indicate that prolonged stimulation of AZF cells by corticotropin, as occurs during long-term stress or disease, may produce pronounced changes in the expression of genes encoding ion channels, thereby reshaping the electrical properties of these cells to enhance or limit cortisol secretion.