Nishimura Masuhiro, Naito Shinsaku, Yokoi Tsuyoshi
Department of Drug Metabolism, Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima.
Drug Metab Pharmacokinet. 2004 Apr;19(2):135-49. doi: 10.2133/dmpk.19.135.
Pairs of forward and reverse primers and TaqMan probes specific to each human nuclear receptor were prepared. Analysis of the mRNA expression level of each target of 43 nuclear receptors in total RNA from single and pooled specimens of various human organs (liver, kidney, adrenal gland, lung, heart, brain, cerebellum, skeletal muscle, spleen, thymus, thyroid gland, prostate, testis, uterus, placenta, bone marrow, trachea, and salivary gland) was performed by real-time reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The mRNA expression of 33 nuclear receptors (NR1A1, 1A2, 1B1, 1B2, 1B3, 1C1, 1C2, 1C3, 1D1, 1D2, 1F1, 1F2, 1F3, 1H2, 1H3, 1I1, 1I2, 2B1, 2B2, 2B3, 2C1, 2C2, 2F1, 2F2, 3A2, 3B1, 3C1, 3C2, 3C4, 4A1, 4A2, 4A3, and 6A1) was successfully detected in all of the tissues by this method. NR1H4, 2A1, and 3C3 mRNAs were not detectable in the heart, heart, and liver, respectively. NR5A2 mRNA was not detectable in either the brain or cerebellum. NR3A1 mRNA was not detectable in the small intestine, colon, brain, and cerebellum. NR5A1 mRNA was not detectable in the kidney, stomach, small intestine, and colon. NR1I3 mRNA was detected in the liver, kidney, stomach, small intestine, adrenal gland, lung, brain, skeletal muscle, thymus, thyroid gland, prostate, testis, placenta, and trachea. NR2A2 mRNA was detected in the liver, kidney, prostate, testis, uterus, and trachea. NR2E1 mRNA was detected in the adrenal gland, brain, cerebellum, testis, placenta, and bone marrow. NR2E3 mRNA was detected in the adrenal gland, thyroid gland, prostate, testis, uterus, trachea, and salivary gland. This study provides information concerning the tissue distribution of the mRNA expression of 43 human nuclear receptors. The mRNA expression profiles of CYP3A4, CYP3A5 and ABC-transporters are also shown. These results are valuable for establishing a nuclear receptor-mediated screening system for new chemical entities in new drug development.
制备了针对每个人类核受体的正向和反向引物对以及TaqMan探针。使用ABI PRISM 7700序列检测系统，通过实时逆转录PCR对来自各种人类器官（肝脏、肾脏、肾上腺、肺、心脏、大脑、小脑、骨骼肌、脾脏、胸腺、甲状腺、前列腺、睾丸、子宫、胎盘、骨髓、气管和唾液腺）的单个和混合样本的总RNA中43种核受体的每个靶标的mRNA表达水平进行了分析。通过该方法成功检测到了所有组织中33种核受体（NR1A1、1A2、1B1、1B2、1B3、1C1、1C2、1C3、1D1、1D2、1F1、1F2、1F3、1H2、1H3、1I1、1I2、2B1、2B2、2B3、2C1、2C2、2F1、2F2、3A2、3B1、3C1、3C2、3C4、4A1、4A2、4A3和6A1）的mRNA表达。NR1H4、2A1和3C3的mRNA分别在心脏、心脏和肝脏中未检测到。NR5A2的mRNA在大脑或小脑中均未检测到。NR3A1的mRNA在小肠、结肠、大脑和小脑中未检测到。NR5A1的mRNA在肾脏、胃、小肠和结肠中未检测到。NR1I3的mRNA在肝脏、肾脏、胃、小肠、肾上腺、肺、大脑、骨骼肌、胸腺、甲状腺、前列腺、睾丸、胎盘和气管中检测到。NR2A2的mRNA在肝脏、肾脏、前列腺、睾丸、子宫和气管中检测到。NR2E1的mRNA在肾上腺、大脑、小脑、睾丸、胎盘和骨髓中检测到。NR2E3的mRNA在肾上腺、甲状腺、前列腺、睾丸、子宫、气管和唾液腺中检测到。本研究提供了有关43种人类核受体mRNA表达的组织分布的信息。还展示了CYP3A4、CYP3A5和ABC转运蛋白的mRNA表达谱。这些结果对于在新药开发中建立用于新化学实体的核受体介导的筛选系统具有重要价值。
