Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202-9037, and Department of Physiology and Biophysics, University of Miami, Miller School of Medicine, Miami, Florida 33136.
J Neurosci. 2014 Mar 26;34(13):4686-91. doi: 10.1523/JNEUROSCI.3100-13.2014.
β-Phenylethylamine (βPEA) is a trace amine present in the CNS of all animals tested to date. However, its function is still not fully understood. βPEA has been suggested to function as a neurotransmitter and/or to mimic the effect of amphetamine (Amph). In support of the latter is the observation that βPEA and Amph produce similar but not identical behaviors. Here, we show that βPEA, like Amph, activates the dopamine transporter and the amine-gated chloride channel LGC-55 to generate behaviors in Caenorhabditis elegans. However, although Amph-induced behaviors occurred gradually during 10 min of treatment, βPEA induced maximal effects within 1 min. In vitro data demonstrate that βPEA activates the LGC-55 more efficiently than Amph (Km = 9 and 152 μm, respectively) and generates saturating currents that are 10 times larger than those produced by Amph. These results suggest that activation of LGC-55 mostly accounts for the behavioral effects reached after 1 min of treatment with βPEA. Importantly, our in vitro and in vivo data show that Amph increases the effects induced by βPEA on the LGC-55, indicating that Amph potentiates the effects generated by the biogenic amine βPEA. Together, our data not only identify a new target for βPEA, but also offer a novel mechanism of action of Amph. In addition, our results highlight C. elegans as a powerful genetic model for studying the effects of biogenic and synthetic amines both at the molecular and behavioral levels.
β-苯乙胺（βPEA）是迄今为止在所有测试动物的中枢神经系统中存在的痕量胺。然而，其功能尚未完全了解。βPEA 被认为具有神经递质的作用，并且/或者可以模拟安非他命（Amph）的作用。支持后一种观点的是观察到βPEA 和 Amph 产生相似但不完全相同的行为。在这里，我们表明，βPEA 与 Amph 一样，激活多巴胺转运体和胺门控氯离子通道 LGC-55，从而在秀丽隐杆线虫中产生行为。然而，尽管 Amph 诱导的行为在 10 分钟的治疗过程中逐渐发生，但βPEA 在 1 分钟内诱导最大效应。体外数据表明，βPEA 比 Amph 更有效地激活 LGC-55（Km 值分别为 9 和 152μm），并产生比 Amph 产生的饱和电流大 10 倍的电流。这些结果表明，LGC-55 的激活主要解释了βPEA 治疗 1 分钟后达到的行为效应。重要的是，我们的体外和体内数据表明，Amph 增加了βPEA 对 LGC-55 的诱导作用，表明 Amph 增强了生物胺βPEA 产生的作用。总之，我们的数据不仅确定了βPEA 的新靶标，而且提供了 Amph 作用的新机制。此外，我们的结果强调秀丽隐杆线虫作为一种强大的遗传模型，可用于研究生物胺和合成胺在分子和行为水平上的作用。
