Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia.
Institute of Experimental Medicine, 197376 Saint Petersburg, Russia.
Int J Mol Sci. 2021 Jul 7;22(14):7307. doi: 10.3390/ijms22147307.
Trace amine-associated receptors (TAARs) are a group of G protein-coupled receptors that are expressed in the olfactory epithelium, central nervous system, and periphery. TAAR family generally consists of nine types of receptors (TAAR1-9), which can detect biogenic amines. During the last 5 years, the TAAR5 receptor became one of the most intriguing receptors in this subfamily. Recent studies revealed that TAAR5 is involved not only in sensing socially relevant odors but also in the regulation of dopamine and serotonin transmission, emotional regulation, and adult neurogenesis by providing significant input from the olfactory system to the limbic brain areas. Such results indicate that future antagonistic TAAR5-based therapies may have high pharmacological potential in the field of neuropsychiatric disorders. TAAR5 is known to be expressed in leucocytes as well. To evaluate potential hematological side effects of such future treatments we analyzed several hematological parameters in mice lacking TAAR5. In these mutants, we observed minor but significant changes in the osmotic fragility test of erythrocytes and hematocrit levels. At the same time, analysis of other parameters including complete blood count and reticulocyte levels showed no significant alterations in TAAR5 knockout mice. Thus, TAAR5 gene knockout leads to minor negative changes in the erythropoiesis or eryptosis processes, and further research in that field is needed. The impact of TAAR5 deficiency on other hematological parameters seems minimal. Such negative, albeit minor, effects of TAAR5 deficiency should be taken into account during future TAAR5-based therapy development.
痕量胺相关受体(TAARs)是一组表达在嗅上皮、中枢神经系统和外周的 G 蛋白偶联受体。TAAR 家族一般由九种受体(TAAR1-9)组成,它们可以检测生物胺。在过去的 5 年中,TAAR5 受体成为该亚家族中最引人注目的受体之一。最近的研究表明,TAAR5 不仅参与感知与社交相关的气味,而且通过提供来自嗅觉系统对边缘大脑区域的重要输入,调节多巴胺和 5-羟色胺的传递、情绪调节和成年神经发生。这些结果表明,未来基于 TAAR5 的拮抗疗法在神经精神疾病领域可能具有很高的药理学潜力。TAAR5 也已知在白细胞中表达。为了评估此类未来治疗方法的潜在血液学副作用,我们在缺乏 TAAR5 的小鼠中分析了几种血液学参数。在这些突变体中,我们观察到红细胞渗透脆性试验和血细胞比容水平有轻微但显著的变化。同时,对包括全血细胞计数和网织红细胞水平在内的其他参数的分析表明,TAAR5 基因敲除小鼠没有明显的改变。因此,TAAR5 基因敲除导致红细胞生成或红细胞生成过程中的轻微负变化,需要进一步研究该领域。TAAR5 缺乏对其他血液学参数的影响似乎很小。在未来基于 TAAR5 的治疗开发中,应考虑 TAAR5 缺乏的这些负面但轻微的影响。