Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

Natasa Spasojevic,Predrag Jovanovic,Sladjana Dronjak

doi:10.1590/0001-3765201520130400

Natasa Spasojevic, Predrag Jovanovic + Show 1 more

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https://doi.org/10.1590/0001-3765201520130400

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Abstract

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Highlights

The syndrome of major depression, the melancholic type, potentially reflects dysregulation of the stress response (Chrousos and Gold 1998)
The results presented in Fig. 3. indicate a major influence of chronic unpredictable mild stress (CUMS) (F(1,16) = 17.94, p
CUMS led to increased Tyrosine hydroxylase (TH) mRNA levels in the adrenal medulla

Summary

Introduction

The syndrome of major depression, the melancholic type, potentially reflects dysregulation of the stress response (Chrousos and Gold 1998). Several studies indicate that VMATs play a critical role in sorting, storing and releasing of monoamines, and in fine-tuning of neuronal and endocrine informational output (Henry et al 1994, Eiden et al 2004). Two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) have been characterized in rodent tissue (Erickson et al 1992). VMAT1 is widely expressed in all adrenal chromaffin cells, while VMAT2 is colocalized with TH enzyme (Tillinger et al 2010). A subpopulation of chromogranin A -expressing chromaffin cells of the adrenal medulla express VMAT2 (Weihe et al 1994). Chromogranins are highly efficient systems directly involved in monoamine accumulation and in the exocytotic release of catecholamines (Borges et al 2010)

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