Neuroscience Program, Department of Psychology, Colgate University, Hamilton, NY 13346, USA
J Exp Biol. 2018 Oct 4;221(Pt 19):jeb184838. doi: 10.1242/jeb.184838.
Invertebrate receptors for the neurotransmitter serotonin (5-HT) have been identified in numerous species from diverse phyla, including Arthropoda, Mollusca, Nematoda and Platyhelminthes. For many receptors, cloning and characterization in heterologous systems have contributed data on molecular structure and function across both closely and distantly related species. This article provides an overview of heterologously expressed receptors, and considers evolutionary relationships among them, classification based on these relationships and nomenclature that reflects classification. In addition, transduction pathways and pharmacological profiles are compared across receptor subtypes and species. Previous work has shown that transduction mechanisms are well conserved within receptor subtypes, but responses to drugs are complex. A few ligands display specificity for different receptors within a single species; however, none acts with high specificity in receptors across different species. Two non-selective vertebrate ligands, the agonist 5-methoxytryptamine and antagonist methiothepin, are active in most receptor subtypes in multiple species and hence bind very generally to invertebrate 5-HT receptors. Future challenges for the field include determining how pharmacological profiles are affected by differences in species and receptor subtype, and how function in heterologous receptors can be used to better understand 5-HT activity in intact organisms.
无脊椎动物对神经递质 5-羟色胺（5-HT）的受体已在包括节肢动物、软体动物、线虫和扁形动物在内的众多不同门的物种中被鉴定出来。对于许多受体，在异源系统中的克隆和表征为密切和远缘相关物种的分子结构和功能提供了数据。本文概述了异源表达的受体，并考虑了它们之间的进化关系、基于这些关系的分类以及反映分类的命名法。此外，还比较了跨受体亚型和物种的转导途径和药理学特征。以前的工作表明，转导机制在受体亚型内很好地保守，但对药物的反应很复杂。少数配体在同一物种内的不同受体上显示出特异性；然而，没有一种在不同物种的受体上具有高度特异性。两种非选择性脊椎动物配体，激动剂 5-甲氧基色胺和拮抗剂甲硫哒嗪，在多个物种的大多数受体亚型中都具有活性，因此非常普遍地结合无脊椎动物 5-HT 受体。该领域未来的挑战包括确定物种和受体亚型差异如何影响药理学特征，以及异源受体中的功能如何用于更好地理解完整生物体中的 5-HT 活性。
