Department of Anatomy and Neurobiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Laboratory of Veterinary Anatomy, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan.
Neuroreport. 2020 Feb 5;31(3):274-280. doi: 10.1097/WNR.0000000000001416.
Organic cation transporters (OCTs) are poly-specific carriers for endogenous and exogenous cationic compounds. These are widely distributed in the nervous system and mediate neuronal activities. As antineoplastic cationic drugs accumulate in the dorsal root ganglion (DRG), OCT function has been studied mainly in cultured DRG neurons. However, the histological distribution of OCTs in the DRG is unclear. This study investigated the localization of OCT2 (a member of OCTs) in mouse DRG neurons and determined their histochemical properties. OCT2 expression was found in about 20% of DRG neurons, which were small to medium size. OCT2-expressing neurons were labeled with markers for peptidergic nociceptive (substance P or calcitonin gene-related peptide) and tactile/proprioceptive (neurofilament 200 or tropomyosin receptor kinase B or C) neurons. OCT2 was also expressed in cholinergic DRG neurons identified by choline acetyltransferase promoter-derived Cre expression. In the spinal dorsal horn, OCT2 was distributed in superficial to deep laminae. OCT2 immunoreactivity was punctate in appearance and localized in the nerve terminals of sensory afferents with labeling of neurochemical markers. Our findings suggest that OCT2 as a low-affinity, high-capacity carrier may take up substrates including cationic neurotransmitters and drugs from the extracellular space around cell bodies in DRG neurons.
有机阳离子转运体(OCTs)是内源性和外源性阳离子化合物的多特异性载体。这些广泛分布于神经系统,并调节神经元活动。由于抗肿瘤阳离子药物在背根神经节(DRG)中积累,因此 OCT 的功能主要在培养的 DRG 神经元中进行研究。然而,DRG 中 OCT 的组织分布尚不清楚。本研究调查了 OCT2(OCTs 的一个成员)在小鼠 DRG 神经元中的定位,并确定了它们的组织化学特性。发现 OCT2 表达于约 20%的 DRG 神经元中,这些神经元为中小体型。表达 OCT2 的神经元被肽能伤害感受(P 物质或降钙素基因相关肽)和触觉/本体感觉(神经丝 200 或原肌球蛋白受体激酶 B 或 C)神经元的标志物标记。OCT2 也存在于由胆碱乙酰转移酶启动子衍生的 Cre 表达鉴定的胆碱能 DRG 神经元中。在脊髓背角,OCT2 分布于浅层至深层。OCT2 免疫反应呈点状外观,定位于感觉传入神经末梢,标记神经化学标志物。我们的发现表明,OCT2 作为一种低亲和力、高容量载体,可能从 DRG 神经元细胞体周围细胞外空间摄取包括阳离子神经递质和药物在内的底物。