Distribution of organic cation transporter 3, a corticosterone‐sensitive monoamine transporter, in the rat brain

Abstract

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates bidirectional, sodium-independent transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine. OCT3-mediated transport is directly inhibited by corticosterone, suggesting a potential role for the transporter in mediating some of the effects of stress and glucocorticoids on monoaminergic neurotransmission. To elucidate the importance of OCT3 in clearance of extracellular monoamines in the brain, we used immunohistochemical techniques to describe the distribution of OCT3-like-immunoreactive (OCT3-ir) cells throughout the rostrocaudal extent of adult male rat brains. OCT3-ir cell bodies were widely distributed throughout the brain, with the highest densities observed in the superior and inferior colliculi, islands of Calleja, subiculum, lateral septum, lateral and dorsomedial hypothalamic nuclei, and granule cell layers of the main and accessory olfactory bulbs, the cerebellum, and the retrosplenial granular cortex. OCT3-ir cells and/or fibers were also observed in circumventricular organs, and OCT3-ir ependymal cells were observed in the linings of all cerebral ventricles. The widespread distribution of OCT3-ir cell bodies, including regions receiving dense monoaminergic projections, suggests an important role for this transporter in regulating extracellular concentrations of monoamines in the rat brain and is consistent with the hypothesis that corticosterone-induced inhibition of OCT3-mediated transport may contribute to effects of acute stress or corticosterone on monoaminergic neurotransmission.

Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3

“…Addressing the issue of regional vulnerability is beyond the scope of this study; however, Oct3 −/− mice may provide a useful model to study PQ toxicity when damage to both DA terminals and cell bodies is desired. It is worthwhile to note that Oct3 immunoreactivity has been reported to be higher in the striatum than in the niga (13). A lower level of Oct3 (and hence, less buffering capacity) in combination with a high microglia population in the nigra might contribute to a higher sensitivity of the DA cell body compared with DA terminals when treated with PQ.…”

“…Blocking DAT function abolished PQ + neurotoxicity in both cells and living mice. In addition to DAT, PQ + is also a substrate for the organic cation transporter-3 (Oct3), a bidirectional transporter that is highly expressed in astrocytes and GABAergic neurons in the nigrostriatal regions (12,13). Together, these two transporters function in a concerted manner to mediate nigrostriatal damage.…”

Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

“…Non-specific organic cation transporters (OCTs) are expressed throughout the BNST (Gasser et al, 2009). The high-capacity, low-affinity OCT3 is thought to act as a secondary means of norepinephrine clearance, and is inhibited by physiological levels of corticosterone (Gasser et al, 2006).…”

Selective Transport of Monoamine Neurotransmitters by Human Plasma Membrane Monoamine Transporter and Organic Cation Transporter 3

“…OCT3 and PMAT have been reported to be expressed in the brain and a number of peripheral tissues (Slitt et al, 2002;Engel et al, 2004). In rodent brains, in situ hybridization and immunolocalization work suggested that Oct3 and Pmat are expressed in neuronal cells in many brain regions (Amphoux et al, 2006;Dahlin et al, 2007;Gasser et al, 2009). Oct3 is also reported to be expressed in astroglial cells (Cui et al, 2009;Gasser et al, 2009).…”