Department of Human Molecular Genetics, University of Heidelberg, Germany.
J Comp Neurol. 2011 Feb 15;519(3):420-32. doi: 10.1002/cne.22525.
Since the first description of 5-HT₃ receptors more than 50 years ago, there has been speculation about the molecular basis of their receptor heterogeneity. We have cloned the genes encoding novel 5-HT3 subunits 5-HT3C, 5-HT3D, and 5-HT3E and have shown that these subunits are able to form functional heteromeric receptors when coexpressed with the 5-HT3A subunit. However, whether these subunits are actually expressed in human tissue remained to be confirmed. In the current study, we performed immunocytochemistry to locate the 5-HT3A as well as the 5-HT3C, 5-HT3D, and 5-HT3E subunits within the human colon. Western blot analysis was used to confirm subunit expression, and RT-PCR was employed to detect transcripts encoding 5-HT₃ receptor subunits in microdissected tissue samples. This investigation revealed, for the first time, that 5-HT3C, 5-HT3D, and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric neurons. Furthermore, 5-HT3A and 5-HT3D were found to be expressed in submucosal plexus of the human large intestine. These data provide a strong basis for future studies of the roles that specific 5-HT₃ receptor subtypes play in the function of the enteric and central nervous systems and the contribution that specific 5-HT₃ receptors make to the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome and dyspepsia.
自 5-羟色胺 3（5-HT₃）受体被首次描述以来，已有超过 50 年的历史，人们一直推测其受体异质性的分子基础。我们已经克隆了编码新型 5-HT3 亚基 5-HT3C、5-HT3D 和 5-HT3E 的基因，并表明这些亚基与 5-HT3A 亚基共表达时能够形成功能性异源受体。然而，这些亚基是否实际上在人体组织中表达仍有待证实。在当前的研究中，我们进行了免疫细胞化学实验，以定位人类结肠中的 5-HT3A 以及 5-HT3C、5-HT3D 和 5-HT3E 亚基。我们使用 Western blot 分析来确认亚基表达，并采用 RT-PCR 检测微切割组织样本中编码 5-HT₃ 受体亚基的转录本。这项研究首次揭示了 5-HT3C、5-HT3D 和 5-HT3E 亚基与肠肌神经元的 5-HT3A 亚基在细胞体中共表达。此外，还发现 5-HT3A 和 5-HT3D 在人类大肠的黏膜下神经丛中表达。这些数据为未来研究特定 5-HT₃ 受体亚型在肠和中枢神经系统功能中的作用以及特定 5-HT₃ 受体对胃肠道疾病（如肠易激综合征和消化不良）病理生理学的贡献提供了坚实的基础。
