Institute of Biochemistry, Leipzig University, 04103 Leipzig, Germany.
Institute of Biological Information Processing, IBI-1, Research Center Jülich, 52428 Jülich, Germany.
Int J Mol Sci. 2022 Jan 31;23(3):1677. doi: 10.3390/ijms23031677.
Biogenic amines constitute an important group of neuroactive substances that control and modulate various neural circuits. These small organic compounds engage members of the guanine nucleotide-binding protein coupled receptor (GPCR) superfamily to evoke specific cellular responses. In addition to dopamine- and 5-hydroxytryptamine (serotonin) receptors, arthropods express receptors that are activated exclusively by tyramine and octopamine. These phenolamines functionally substitute the noradrenergic system of vertebrates Octopamine receptors that are the focus of this study are classified as either α- or β-adrenergic-like. Knowledge on these receptors is scarce for the American cockroach (). So far, only an α-adrenergic-like octopamine receptor that primarily causes Ca release from intracellular stores has been studied from the cockroach (PaOctα1R). Here we succeeded in cloning a gene from cockroach brain tissue that encodes a β-adrenergic-like receptor and leads to cAMP production upon activation. Notably, the receptor is 100-fold more selective for octopamine than for tyramine. A series of synthetic antagonists selectively block receptor activity with epinastine being the most potent. Bioinformatics allowed us to identify a total of 19 receptor sequences that build the framework of the biogenic amine receptor clade in the American cockroach. Phylogenetic analyses using these sequences and receptor sequences from model organisms showed that the newly cloned gene is an β2-adrenergic-like octopamine receptor. The functional characterization of PaOctβ2R and the bioinformatics data uncovered that the monoaminergic receptor family in the hemimetabolic is similarly complex as in holometabolic model insects like and the honeybee, . Thus, investigating these receptors in detail may contribute to a better understanding of monoaminergic signaling in insect behavior and physiology.
生物胺是一类重要的神经活性物质，它们控制和调节各种神经回路。这些小分子有机化合物与鸟嘌呤核苷酸结合蛋白偶联受体（GPCR）超家族的成员结合，引发特定的细胞反应。除了多巴胺和 5-羟色胺（血清素）受体外，节肢动物还表达仅被酪胺和章鱼胺激活的受体。这些酚胺在功能上替代了脊椎动物的去甲肾上腺素能系统。章鱼胺受体是本研究的焦点，它们被分为α-或β-肾上腺素样。关于这些受体的知识对于美洲蟑螂（）来说是稀缺的。到目前为止，仅从蟑螂中研究了一种主要导致细胞内储存的 Ca 释放的α-肾上腺素样章鱼胺受体（PaOctα1R）。在这里，我们成功地从蟑螂脑组织中克隆了一个基因，该基因编码一种β-肾上腺素样受体，在激活时导致 cAMP 产生。值得注意的是，该受体对章鱼胺的选择性比酪胺高 100 倍。一系列合成拮抗剂选择性地阻断受体活性，其中以表那斯汀最为有效。生物信息学使我们能够鉴定总共 19 个受体序列，这些序列构成了美洲蟑螂生物胺受体分支的框架。使用这些序列和来自模式生物的受体序列进行系统发育分析表明，新克隆的基因是一种β2-肾上腺素样章鱼胺受体。PaOctβ2R 的功能表征和生物信息学数据揭示了半变态昆虫中的单胺能受体家族与象鼻虫和蜜蜂等完全变态模式昆虫一样复杂。因此，详细研究这些受体可能有助于更好地理解昆虫行为和生理学中的单胺能信号。
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