Blenau Wolfgang, Daniel Stöppler, Balfanz Sabine, Thamm Markus, Baumann Arnd
Cologne Biocenter and Zoological Institute, University of CologneCologne, Germany.
Department of NMR-Supported Structural Biology, Leibniz-Institut für Molekulare PharmakologieBerlin, Germany.
Front Syst Neurosci. 2017 May 11;11:28. doi: 10.3389/fnsys.2017.00028. eCollection 2017.
Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In , a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT, Dm5-HT, and Dm5-HT couple to cAMP signaling cascades, the Dm5-HT receptor leads to Ca signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth gene was uncovered coding for a Dm5-HT receptor. Knowledge about this receptor's pharmacological properties is very limited. This is quite surprising because Dm5-HT has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT's pharmacology, we evaluated the receptor's response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT signaling and .
血清素（5-羟色胺，5-HT）是原口动物（如昆虫）和后口动物（如哺乳动物）生理和行为过程的重要调节因子。在昆虫中，已发现血清素可调节心率、控制分泌过程、发育、昼夜节律、攻击行为，并有助于学习和记忆。血清素通过与特定膜受体结合并激活来发挥其活性。这些受体绝大多数属于G蛋白偶联受体超家族。在[具体昆虫名称未给出]中，总共鉴定出五个编码5-HT受体的基因。到目前为止，该蛋白质家族中的四个已在药理学上进行了更详细的研究。虽然Dm5-HT、Dm5-HT和Dm5-HT与cAMP信号级联反应偶联，但Dm5-HT受体以依赖肌醇-1,4,5-三磷酸的方式导致Ca信号传导。基于与其他昆虫同源基因的序列相似性，发现了第五个编码Dm5-HT受体的基因。关于该受体药理学特性的知识非常有限。这相当令人惊讶，因为基于对其基因表达的遗传干扰，Dm5-HT已被归因于不同的生理功能。已描述了降低幼虫心脏对5-HT反应的突变，血细胞中Dm5-HT mRNA的特异性敲低导致果蝇对细菌感染的易感性更高。为了更深入地了解Dm5-HT的药理学，我们在基于细胞的功能测定中评估了该受体对一系列已确立的5-HT受体激动剂和拮抗剂的反应。甲氧氯普胺和米安色林被鉴定为两种有效的拮抗剂，它们可能允许对Dm5-HT信号传导进行药理学干扰[具体干扰情况未明确给出]。
