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Brain Struct Funct (2017) 222:19131928 DOI 10.1007/s00429-016-1315-9
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Organic cation transporter 3 (OCT3) is localized to intracellular and surface membranes in select glial and neuronal cellswithin the basolateral amygdaloid complex of both rats and mice
Paul J. Gasser1 Matthew M. Hurley1 June Chan2 Virginia M. Pickel2
Received: 2 June 2016 / Accepted: 16 September 2016 / Published online: 22 September 2016 Springer-Verlag Berlin Heidelberg 2016
Abstract Organic cation transporter 3 (OCT3) is a high-capacity, low-afnity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunouorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. OCT3-immunoreactivity was observed in both glial and neuronal perikarya in both rat and mouse amygdala. Electron microscopic immunolabeling revealed plasma membrane-associated OCT3 immunoreactivity on axonal, dendritic, and astrocytic processes adjacent to a variety of synapses, as well as on neuronal somata. In addition to plasma membrane sites, OCT3 immunolabeling was also observed associated with neuronal and glial endomembranes, including Golgi, mitochondrial and nuclear membranes. Particularly prominent labeling of the outer nuclear membrane was observed in neuronal, astrocytic, microglial
and endothelial perikarya. The localization of OCT3 to neuronal and glial plasma membranes adjacent to synaptic sites is consistent with an important role for this transporter in regulating the amplitude, duration, and physical spread of released monoamines, while its localization to mitochondrial and outer nuclear membranes suggests previously undescribed roles for the transporter in the intracellular disposition of monoamines.
Keywords Monoamine Ultrastructure Corticosterone
Serotonin Norepinephrine Dopamine Histamine
Clearance Uptake Stress
Introduction
A critical step in the regulation of monoaminergic neuro-transmission is the clearance of released transmitters from the extracellular space, limiting the duration and physical spread of monoamine signals, and thus determining the activation of receptors on target cells (Rice and Cragg 2008). Monoamine clearance has been attributed primarily to the high-afnity,...