Fukuda Nobuhiko, Naito Saki, Masukawa Daiki, Kaneda Moemi, Miyamoto Hiroshi, Abe Takaya, Yamashita Yui, Endo Itaru, Nakamura Fumio, Goshima Yoshio
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Brain Res. 2015 Mar 30;1602:62-74. doi: 10.1016/j.brainres.2015.01.020. Epub 2015 Jan 16.
Oa1 is the casual gene for ocular albinism-1 in humans. The gene product OA1, alternatively designated as GPR143, belongs to G-protein coupled receptors. It has been reported that OA1 is a specific receptor for 3, 4-dihydroxy- L-phenylalanine (DOPA) in retinal pigmental epithelium where DOPA facilitates the pigmentation via OA1 stimulation. We have recently shown that OA1 mediates DOPA-induced depressor response in rat nucleus tractus solitarii. However, the distribution and function of OA1 in other regions are largely unknown. We have generated oa1 knockout mice and examined OA1 expression in both neuronal and non-neuronal tissues by immunohistochemical analyses using anti-mouse OA1 monoclonal antibodies. In the telencephalon, OA1 was expressed in cerebral cortex and hippocampus. Predominant expression of OA1 was observed in the pyramidal neurons in these regions. OA1 was also expressed in habenular nucleus, hypothalamus, substantia nigra, and medulla oblongata. The expression of OA1 in the nucleus tractus solitarii of medulla oblongata may support the reduction of blood pressure by the microinjection of DOPA into this region. Outside of the nervous system, OA1 was expressed in heart, lung, liver, kidney and spleen. Abundant expression was observed in the renal tubules and the splenic capsules. These peripheral regions are innervated by numerous sympathetic nerve endings. In addition, substantia nigra contains a large population of dopaminergic neurons. Thus, the immunohistochemical analyses suggest that OA1 may modulate the monoaminergic functions in both peripheral and central nervous systems.
Oa1是人类眼部白化病1型的致病基因。该基因产物OA1，也被称为GPR143，属于G蛋白偶联受体。据报道，OA1是视网膜色素上皮细胞中3,4 - 二羟基-L-苯丙氨酸（DOPA）的特异性受体，在该细胞中DOPA通过刺激OA1促进色素沉着。我们最近发现OA1介导大鼠孤束核中DOPA诱导的降压反应。然而，OA1在其他区域的分布和功能在很大程度上尚不清楚。我们制备了oa1基因敲除小鼠，并使用抗小鼠OA1单克隆抗体通过免疫组织化学分析检测了OA1在神经元和非神经元组织中的表达。在端脑中，OA1在大脑皮层和海马体中表达。在这些区域的锥体神经元中观察到OA1的主要表达。OA1也在缰核、下丘脑、黑质和延髓中表达。OA1在延髓孤束核中的表达可能支持通过向该区域微量注射DOPA来降低血压。在神经系统之外，OA1在心脏、肺、肝脏、肾脏和脾脏中表达。在肾小管和脾包膜中观察到丰富的表达。这些外周区域由大量交感神经末梢支配。此外，黑质含有大量多巴胺能神经元。因此，免疫组织化学分析表明OA1可能在外周和中枢神经系统中调节单胺能功能。
