Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
School of Pharmacy and Bioengineering, Keele University, Keele, United Kingdom.
Methods Enzymol. 2020;637:513-538. doi: 10.1016/bs.mie.2020.03.012. Epub 2020 Apr 17.
The retinoic acid (RA) signaling pathway is crucial for the control of embryonic development and also regulates function of several organ systems in the adult, including the central nervous system. The retinoic acid receptors (RARs) that mediate the majority of the functions of RA can promote proliferation, differentiation, morphogenesis and cell survival. Dysregulation of this signaling pathway has been considered in the pathophysiology of various diseases including neurodegenerative disorders such Alzheimer's disease and amyotrophic lateral sclerosis. Thus, drugs targeted to the RARs have been proposed as treatments for such diseases. Understanding how these drugs distribute in the body is essential to determine their potential effectiveness. However measuring tissue levels of what are often lipophilic drugs can be difficult. Here we describe an indirect measurement of RAR ligand tissue distribution after intraperitoneal injection into rodents that uses a sensitive RA reporter cell line.
视黄酸（RA）信号通路对于胚胎发育的控制至关重要，也调节成年后几个器官系统的功能，包括中枢神经系统。介导 RA 的大部分功能的视黄酸受体（RARs）可以促进增殖、分化、形态发生和细胞存活。这种信号通路的失调已被认为是各种疾病的病理生理学中的一个因素，包括神经退行性疾病，如阿尔茨海默病和肌萎缩性侧索硬化症。因此，靶向 RAR 的药物已被提议作为这些疾病的治疗方法。了解这些药物在体内的分布对于确定它们的潜在效果至关重要。然而，通常亲脂性药物的组织水平的测量可能很困难。在这里，我们描述了一种在啮齿动物中经腹腔注射后间接测量 RAR 配体组织分布的方法，该方法使用了一种敏感的 RA 报告细胞系。
