(R)-Octopamine (OA), a major invertebrate biogenic amine, plays an important role in a wide variety of physiological processes as a neurohormone, neuromodulator, and neurotransmitter in insects. OA receptors (OARs) are class A G protein-coupled receptors that specifically bind OA to activate downstream signaling cascades by coupling to G proteins and presumably other regulatory proteins. These receptors are broadly classified as α- and β-adrenergic-like OARs (α- and β-ALOARs). OARs are considered important targets of insecticides and acaricides. In the present study, we examined the actions of an array of 13 heterocyclic OAR agonists with the moieties that correspond to the phenyl group and the basic nitrogen atom of OA on α- and β-ALOARs from the silkworm (Bombyx mori) and the signaling pathways activated through these actions. The results indicated that these compounds display structure-dependent receptor subtype selectivity and G protein subtype preference, underscoring the need to determine which subtype and signaling pathway mediates toxicologically relevant effects for the efficient discovery of novel pest control chemicals. The results of insecticidal assays using B. mori larvae suggested that the activation of signal transduction pathways via α-ALOARs might be mainly responsible for the toxicological effects of the heterocycles.

( R )-Octopamine (OA) 是一种主要的无脊椎动物生物胺，作为昆虫的神经激素、神经调节剂和神经递质，在多种生理过程中发挥着重要作用。OA 受体 (OAR) 是 AG 类蛋白偶联受体，通过与 G 蛋白和可能的其他调节蛋白偶联，特异性结合 OA 以激活下游信号级联。这些受体大致分为α-和β-肾上腺素能样OAR（α-和β-ALOAR）。OARs被认为是杀虫剂和杀螨剂的重要目标。在本研究中，我们检查了一系列 13 种杂环 OAR 激动剂的作用，这些激动剂的部分对应于 OA 的苯基和碱性氮原子对家蚕 ( Bombyx mori) 和通过这些作用激活的信号通路。结果表明，这些化合物显示出结构依赖性受体亚型选择性和 G 蛋白亚型偏好，强调需要确定哪种亚型和信号通路介导毒理学相关效应，以有效发现新型害虫防治化学品。使用家蚕幼虫进行杀虫试验的结果表明，通过 α-ALOARs 激活信号转导途径可能是杂环化合物毒理学作用的主要原因。