Department of Biomedical Sciences, Marquette University, Milwaukee, WI, USA.
Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Handb Exp Pharmacol. 2021;266:241-251. doi: 10.1007/164_2021_493.
Corticosteroid hormones exert powerful influences on neuronal physiology and behavior by activating intracellular glucocorticoid receptors (GR) and mineralocorticoid receptors (MR), which act as ligand-gated transcription factors, altering gene expression. In addition to these genomic effects on physiology and behavior, which are usually delayed by minutes to hours, corticosteroid hormones also initiate rapid effects through diverse nongenomic mechanisms. One such mechanism involves the direct inhibition by corticosteroid hormones of monoamine transport mediated by the "uptake" transporter, organic cation transporter 3 (OCT3), a high-capacity, low-affinity transporter for norepinephrine, epinephrine, dopamine, serotonin, and histamine. In this review we describe studies that demonstrate OCT3 expression and corticosterone-sensitive monoamine transport in the brain and present evidence supporting the hypothesis that corticosterone exerts rapid, nongenomic actions on glia and neurons, ultimately modulating physiology and behavior, by inhibiting OCT3-mediated monoamine clearance. We also describe the corticosteroid sensitivity of the other members of the uptake family and examine their potential contributions to nongenomic effects of corticosteroids in the brain.
皮质甾类激素通过激活细胞内的糖皮质激素受体 (GR) 和盐皮质激素受体 (MR) 对神经元的生理和行为产生强大的影响，这两种受体作为配体门控转录因子，改变基因表达。除了这些对生理和行为的基因组效应（通常延迟数分钟到数小时）外，皮质甾类激素还通过多种非基因组机制引发快速效应。其中一种机制涉及皮质甾类激素对单胺转运的直接抑制，由“摄取”转运体有机阳离子转运体 3 (OCT3) 介导，OCT3 是一种高容量、低亲和力的去甲肾上腺素、肾上腺素、多巴胺、血清素和组胺转运体。在这篇综述中，我们描述了证明大脑中 OCT3 表达和皮质甾酮敏感的单胺转运的研究，并提供了支持以下假设的证据，即皮质甾酮通过抑制 OCT3 介导的单胺清除，对神经胶质细胞和神经元产生快速的非基因组作用，最终调节生理和行为。我们还描述了摄取家族的其他成员对皮质甾类激素的糖皮质激素敏感性，并研究了它们对大脑中皮质甾类激素非基因组效应的潜在贡献。
