BRAIN DISTRIBUTION OF RHESUS MONKEY TRACE AMINE RECEPTORS TA1 AND TA4

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。痕量胺类化合物，包括酪胺、色胺、章鱼胺和β-苯乙胺，是结构上与经典生物胺相关的内源胺类化合物。痕量胺受体的发现为研究痕量胺的功能和药理机制提供了新的契机。本实验室已从恒河猴中克隆了两个示踪胺受体亚型，rh TA1和rh TA4，它们在结构上与人TA1和TA4有96%的相似性，但与啮齿动物受体有所不同。这种高度的相似性表明，恒河猴非常适合研究与人类疾病相关的痕量胺受体生物学和病理学，如精神分裂症、多动症和成瘾。为了探讨微量胺受体蛋白在脑内的分布，我们使用市售抗体(亲和力生物试剂)用Western blotting方法检测了恒河猴不同脑区的重组人TA1和重组人TA4蛋白。结果：在大脑皮层、眶前叶皮质、内侧前额叶皮质、丘脑、海马体、小脑、下丘脑、杏仁核、黑质、苍白球和腹侧被盖区均有表达。讨论：rh TA1和rh TA4的分布与已报道的哺乳动物脑内痕量胺的分布、痕量胺结合部位和痕量胺受体mRNA的分布相一致。人与猴的结构相似，而啮齿类动物的示踪胺受体与人相似，这表明猴可以作为研究示踪胺受体的生理和病理相关性的合适模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Trace amines, including tyramine, tryptamine, octopamine and beta-phenylethylamine are endogenous amine compounds structurally related to classical biogenic amines. The discovery of trace amine receptors brings a new opportunity to study functions and pharmacological mechanisms of trace amines. Our laboratory has cloned two trace amine receptor subtypes from rhesus monkey, rhTA1 and rhTA4, which have 96% structural similarity to human TA1 and TA4 but diverge from the rodent receptors. This high similarity suggests that rhesus monkeys are highly suitable for investigating trace amine receptor biology and pathology relevant to human disorders, such as schizophrenia, ADHD and addiction. To explore the distribution of trace amine receptor protein in brain, we employed Western blotting using commercially available antibodies (Affinity BioReagents) to detect rhTA1 and rhTA4 proteins in different brain regions of rhesus monkey. Results: rhTA1 and rhTA4 were expressed in the following brain regions: cerebral cortex, orbital frontal cortex, medial prefrontal cortex, thalamus, hippocampus, cerebellum, hypothalamus, amygdala, substantia nigra, globus pallidus, and ventral tegmental area. Discussion: The distribution of rhTA1 and rhTA4 parallels the reported distribution of trace amines, trace amine binding sites and trace amine receptor mRNA in mammalian brain. The close structural similarity between human and monkey, but not rodent trace amine receptors indicates that the monkey can serve as an appropriate model for investigating the physiological and pathological relevance of trace amine receptors.