Faculty Collaboration Database

Natural and synthetic corticosteroids inhibit uptake 2-mediated transport in CNS neurons. Physiol Behav 2011 Aug 03;104(2):306-11

Date

11/18/2010

Pubmed ID

21081135

DOI

10.1016/j.physbeh.2010.11.012

Scopus ID

2-s2.0-79958850049 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

In addition to exerting actions via mineralocorticoid and glucocorticoid receptors, corticosteroids also act by inhibiting uptake(2), a high-capacity monoamine transport system originally described in peripheral tissues. Recent studies have demonstrated that uptake(2) transporters are expressed in the brain and play roles in monoamine clearance, suggesting that they mediate some corticosteroid effects on physiological and behavioral processes. However, the sensitivity of brain uptake(2) to many natural and synthetic corticosteroids has not been characterized. Cultured rat cerebellar granule neurons (CGNs) were previously shown to exhibit corticosterone-sensitive accumulation of the uptake(2) substrate 1-methyl-4-phenylpyridinium (MPP(+)). We examined the expression of uptake(1) and uptake(2) transporters in CGNs, and tested the effects of a variety of natural and synthetic corticosteroids on accumulation of [(3)H]-MPP(+) by these cells. Cultured rat CGNs expressed mRNA for three uptake(2)-like transporters: organic cation transporters 1 and 3, and the plasma membrane monoamine transporter. They did not express mRNA for the dopamine or norepinephrine transporters, and expressed very little mRNA for the serotonin reuptake transporter. Accumulation of [(3)H]-MPP(+) by CGNs was dose-dependently inhibited by corticosterone and decynium-22, known inhibitors of uptake(2). Accumulation of MPP(+) was also dose-dependently inhibited, with varying efficacies, by aldosterone, 11-deoxycorticosterone, cortisol, and cortisone, and by the synthetic glucocorticoids betamethasone, dexamethasone and prednisolone, and the glucocorticoid receptor antagonist RU38486. These studies demonstrate that uptake(2) in the CNS is inhibited by a variety of natural and synthetic corticosteroids, and suggest that inhibition of uptake(2)-mediated monoamine clearance may underlie some behavioral and physiological effects of these hormones.

Author List

Hill JE, Makky K, Shrestha L, Hillard CJ, Gasser PJ

Authors

Paul Gasser BS,MS,PhD Assistant Professor in the Biomedical Sciences department at Marquette University
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenal Cortex Hormones
Animals
Animals, Newborn
Cells, Cultured
Cerebellum
Female
Gene Expression Regulation
Inhibitory Concentration 50
Male
Mandelic Acids
Membrane Transport Proteins
Neurons
Quinolines
RNA, Messenger
Rats
Tritium