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小鼠迷走传入神经元中的热敏性瞬时受体电位通道

Thermosensitive transient receptor potential channels in vagal afferent neurons of the mouse.

作者信息

Zhang Lei, Jones Sarahlouise, Brody Kate, Costa Marcello, Brookes Simon J H

机构信息

Department of Human Physiology, and Centre for Neuroscience, Flinders University, Adelaide, South Australia, South Australia, 5001, Australia.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G983-91. doi: 10.1152/ajpgi.00441.2003. Epub 2004 Jan 15.

Abstract

A number of transient receptor potential (TRP) channels has recently been shown to mediate cutaneous thermosensitivity. Sensitivity to warm and cool stimuli has been demonstrated in both human and animal gastrointestinal tract; however, the molecular mechanisms that underlie this have not been determined. Vagal afferent neurons with cell bodies in the nodose ganglion are known to mediate nonnociceptive sensation from the upper gut. In this study, isolated cultured nodose ganglion from the mouse neurons showed changes in cytoplasmic-free Ca(2+) concentrations over a range of temperatures, as well as to icilin (a TRPM8 and TRPN1 agonist) and capsaicin (a TRPV1 agonist). RT-PCR was used to show the presence of six temperature-sensitive TRP channel transcripts (TRPV1-4, TRPN1, and TRPM8) in whole nodose ganglia. In addition, RT-PCR of single nodose cell bodies, which had been retrogradely labeled from the upper gut, detected transcripts for TRPV1, TRPV2, TRPV4, TRPN1, and TRPM8 in a proportion of cells. Immunohistochemical labeling detected TRPV1 and TRPV2 proteins in nodose ganglia. The presence of TRP channel transcripts and proteins was also detected in cells within several regions of the gastrointestinal tract. Our results reveal that TRP channels are present in subsets of vagal afferent neurons that project to the stomach and may confer temperature sensitivity on these cells.

摘要

最近有研究表明,多种瞬时受体电位(TRP)通道可介导皮肤温度敏感性。人类和动物的胃肠道均已证实对温热和冷刺激敏感;然而,其潜在的分子机制尚未明确。已知胞体位于结状神经节的迷走传入神经元可介导来自上消化道的非伤害性感觉。在本研究中,从小鼠神经元分离培养的结状神经节在一定温度范围内以及对艾考糊精(一种TRPM8和TRPN1激动剂)和辣椒素(一种TRPV1激动剂)刺激下,胞质游离Ca(2+)浓度会发生变化。逆转录聚合酶链反应(RT-PCR)用于显示整个结状神经节中存在六种温度敏感的TRP通道转录本(TRPV1 - 4、TRPN1和TRPM8)。此外,对从上消化道逆行标记的单个结状神经节细胞体进行RT-PCR检测,发现部分细胞中存在TRPV1、TRPV2、TRPV4、TRPN1和TRPM8的转录本。免疫组织化学标记在结状神经节中检测到TRPV1和TRPV2蛋白。在胃肠道多个区域的细胞中也检测到了TRP通道转录本和蛋白的存在。我们的研究结果表明,TRP通道存在于投射至胃的迷走传入神经元亚群中,并可能赋予这些细胞温度敏感性。

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