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Organic Cation Transporters and Nongenomic Glucocorticoid Action

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Organic Cation Transporters in the Central Nervous System

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 266))

Abstract

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 “uptake2” 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 uptake2 family and examine their potential contributions to nongenomic effects of corticosteroids in the brain.

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Abbreviations

CeA:

Central nucleus of the amygdala

CNS:

Central nervous system

CPP:

Conditioned place preference

DAT:

Dopamine transporter

DHEA:

Dehydroepiandrosterone

DMH:

Dorsomedial hypothalamus

FSCV:

Fast-scan cyclic voltammetry

GR:

Glucocorticoid receptor

MPP+:

1-Methyl-4-phenylpyridinium

MR:

Mineralocorticoid receptor

NAc:

Nucleus accumbens

NET:

Norepinephrine transporter

OCT1:

Organic cation transporter 1

OCT2:

Organic cation transporter 2

OCT3:

Organic cation transporter 3, also known as slc22a3, solute carrier family 22 (organic cation transporter), serotonin

PMAT:

Plasma membrane monoamine transporter

SERT:

Serotonin transporter

Slc22a3:

Solute carrier family 22 (organic cation transporter), serotonin, also known as organic cation transporter 3

VTA:

Ventral tegmental area

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Correspondence to Paul J. Gasser .

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Benton, K.C., Lowry, C.A., Gasser, P.J. (2021). Organic Cation Transporters and Nongenomic Glucocorticoid Action. In: Daws, L.C. (eds) Organic Cation Transporters in the Central Nervous System. Handbook of Experimental Pharmacology, vol 266. Springer, Cham. https://doi.org/10.1007/164_2021_493

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