Inhibition of gastrin gene expression by somatostatin.
Inhibition of gastrin gene expression by somatostatin.
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DOI：
10.1172/jci113893
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发表时间：
1989-02
期刊：
影响因子：
--
通讯作者：
P. Karnik;S. J. Monahan;M. Wolfe
中科院分区：
文献类型：
--
作者：
P. Karnik;S. J. Monahan;M. Wolfe
在该实验室进行的先前研究表明，含有生长抑素的细胞与胃粘膜中的胃蛋白细胞非常接近，并表明生长抑素对胃蛋白释放产生了局部调节作用。目前的研究旨在确定生长抑素对腹膜胃细胞的影响是否涉及预后事件。生长抑素对胃蛋白mRNA的影响通过DOT印迹杂交使用源自人胃cDNA的胃静脉杂交RNA探针来确定。在孵育培养基中纳入生长抑素会导致稳态胃泌素mRNA的剂量依赖性抑制。相反，当通过在孵育培养基中添加特定的生长抑素抗体对肛门抑制素进行中和时，胃泌素mRNA水平比对照值升高116 +/- 31％（P小于0.01）。总鼻rNA的北印迹杂交表现出一个单个主要条带，分子大小约为620个核苷酸，与预测的胃泌素mRNA的尺寸非常匹配。生长抑素对使用核径流转录测定法检查了生长抑素对胃蛋白基因转录速率的影响。在孵育培养基中包含抗体的生长抑素抗体导致胃蛋白基因转录活性增加33.8 +/- 3.3％（P小于0.01）。这些研究表明，除了对肽释放的确定作用外，生长抑素还对坦率水平上的厌食胃细胞发挥抑制作用。尽管这种抑制作用似乎部分发生在基因转录水平上，但结果也表明生长抑素可能会影响胃泌素mRNA的转录后处理。
Previous studies performed in this laboratory have demonstrated somatostatin-containing cells in close proximity to gastrin cells in antral mucosa and have shown that somatostatin exerts a local regulatory effect on gastrin release. The present studies were directed to determine whether the effects of somatostatin on the antral gastrin cell involve pretranslational events. The effects of somatostatin on gastrin mRNA were determined by dot blot hybridization using a gastrin antisense RNA probe derived from human gastrin cDNA. Inclusion of somatostatin in the incubation medium caused a dose-dependent inhibition of steady-state gastrin mRNA. Conversely, when antral somatostatin was neutralized by the addition of specific somatostatin antibodies to the incubation medium, gastrin mRNA levels increased by 116 +/- 31% over control values (P less than 0.01). Northern blot hybridization of total antral RNA demonstrated a single major band with a molecular size of approximately 620 nucleotides, closely matching the predicted size of gastrin mRNA. The effect of somatostatin on the rate of gastrin gene transcription was examined using nuclear run-off transcription assays. Inclusion of antibodies to somatostatin in the incubation medium resulted in a 33.8 +/- 3.3% increase in gastrin gene transcriptional activity (P less than 0.01). These studies indicate that, in addition to its established effect on peptide release, somatostatin exerts inhibitory effects on antral gastrin cells at the pretranslational level. Although this inhibition appears to occur in part at the gene transcriptional level, the results also indicate that somatostatin may affect posttranscriptional processing of gastrin mRNA.