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大鼠结状神经节细胞中胰高血糖素样肽-1而非葡萄糖依赖性促胰岛素多肽的受体基因表达。

Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells.

作者信息

Nakagawa Atsushi, Satake Hanae, Nakabayashi Hajime, Nishizawa Makoto, Furuya Keisuke, Nakano Shigeru, Kigoshi Toshikazu, Nakayama Kohzo, Uchida Kenzo

机构信息

Department of Internal Medicine, Kanazawa Medical University, Daigaku 1-1, Uchinada 920-0293, Japan.

出版信息

Auton Neurosci. 2004 Jan 30;110(1):36-43. doi: 10.1016/j.autneu.2003.11.001.

Abstract

We previously reported that afferent signals of the rat hepatic vagus increased upon intraportal appearance of insulinotropic hormone glucagon-like peptide-1(7-36) amide (GLP-1), but not glucose-dependent insulinotropic polypeptide (GIP). To obtain molecular evidence for the vagal chemoreception of GLP-1, the concept derived from those electrophysiological observations, receptor gene expressions of GLP-1 and GIP in the rat nodose ganglion were examined by means of reverse transcriptase-mediated polymerase chain reaction (RT-PCR) and Northern blot analysis. Gene expression of the GLP-1 receptor was clearly detected by both RT-PCR and Northern blot analysis. In situ hybridization study confirmed that the expression occurs in neuronal cells of the ganglion. As to the GIP receptor, RT-PCR amplified the gene transcript faintly though Northern blot analysis failed to detect any messages. However, semi-quantitative RT-PCR revealed that the ratio of the gene expression level of the GIP receptor to that of the GLP-1 receptor was less than 1:250, indicating that receptor gene expression of GIP is practically negligible in the ganglion. Additionally, an equal level of GLP-1 receptor gene expressions between left- and right-side ganglia was evidenced by semi-quantitative RT-PCR, implying possible extrahepatic occurrence of vagal GLP-1 reception in addition to the reception through the hepatic vagus (originating from the left-side ganglion). The present results offer, for the first time, the molecular basis for the vagal chemoreception of GLP-1 via its specific receptor.

摘要

我们之前报道过,当促胰岛素激素胰高血糖素样肽-1(7-36)酰胺(GLP-1)经门静脉注入时,大鼠肝迷走神经的传入信号增强,而葡萄糖依赖性促胰岛素多肽(GIP)注入时则不然。为了获得GLP-1迷走化学感受的分子证据,基于那些电生理观察结果提出这一概念,我们通过逆转录介导的聚合酶链反应(RT-PCR)和Northern印迹分析,检测了大鼠结状神经节中GLP-1和GIP的受体基因表达。通过RT-PCR和Northern印迹分析均清楚地检测到了GLP-1受体的基因表达。原位杂交研究证实该表达发生在神经节的神经细胞中。至于GIP受体,RT-PCR微弱地扩增出了基因转录本,不过Northern印迹分析未能检测到任何信息。然而,半定量RT-PCR显示,GIP受体基因表达水平与GLP-1受体基因表达水平之比小于1:250,这表明神经节中GIP的受体基因表达实际上可忽略不计。此外,半定量RT-PCR证明左右侧神经节之间GLP-1受体基因表达水平相当,这意味着除了通过肝迷走神经(起源于左侧神经节)进行感受外,迷走神经对GLP-1的感受可能在肝外发生。本研究结果首次为GLP-1通过其特异性受体进行迷走化学感受提供了分子基础。

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