Structure/Function Relationships in Serotonin Transporter: New Insights from the Structure of a Bacterial Transporter

Rudnick, Gary

doi:10.1007/3-540-29784-7_3

Cited by 25 publications

(17 citation statements)

References 49 publications

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“…In a second set of experiments, preparations were subjected to pre-treatment with aCSF containing fluoxetine, a well-known SERT blocker known to increase 5-HT endogenous levels [22], prior to investigating the PBf responses to acidosis. As applications of fluoxetine at large concentration (100 µM) were reported to double the mean PBf [16], we used weaker concentrations to avoid marked increases of the resting PBf.…”

Section: Resultsmentioning

confidence: 99%

“…Fluoxetine blocks SERT and increases the 5-HT endogenous level and the 5-HT availability at the synaptic cleft [22], [37]. Correlatively, fluoxetine potentiates the facilitation of the RRG by endogenous 5-HT, doubling the resting PBf when applied at 100 µM [16].…”

Section: Discussionmentioning

confidence: 99%

“…In a second set of experiments, the effect of pre-treating the preparations with aCSF(7.4) containing fluoxetine (10 µM or 50 µM; 20 min) was investigated on the RRG response to acidosis. Fluoxetine is a well-known antidepressant of common clinical use that blocks the serotonin transporter (SERT), the blockade of the 5-HT reuptake increasing the 5-HT endogenous levels and potentiating the 5-HT effects at the synaptic cleft [22]. After fluoxetine pre-treatment, the RRG response to acidosis was investigated by subjecting the preparations to aCSF(7.1) containing the same amount of fluoxetine for 5 min.…”

Section: Methodsmentioning

confidence: 99%

“…Using mRNA hybridization and immunohistology, we also report SERT mRNA expression and a few 5-HT neurons in the vicinity of the RTN/pFRG area. As fluoxetine is a commonly used antidepressant known to increase endogenous levels of 5-HT [22], we suggest a cautious use of pharmacological treatments targeting the 5HT system in infants, pregnant women and breastfeeding mothers.…”

Section: Introductionmentioning

confidence: 99%

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Fluoxetine Treatment Abolishes the In Vitro Respiratory Response to Acidosis in Neonatal Mice

Voituron

Shvarev²,

Menuet³

et al. 2010

PLoS ONE

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BackgroundTo secure pH homeostasis, the central respiratory network must permanently adapt its rhythmic motor drive to environment and behaviour. In neonates, it is commonly admitted that the retrotrapezoid/parafacial respiratory group of neurons of the ventral medulla plays the primary role in the respiratory response to acidosis, although the serotonergic system may also contribute to this response.Methodology/Principal FindingsUsing en bloc medullary preparations from neonatal mice, we have shown for the first time that the respiratory response to acidosis is abolished after pre-treatment with the serotonin-transporter blocker fluoxetine (25–50 µM, 20 min), a commonly used antidepressant. Using mRNA in situ hybridization and immunohistology, we have also shown the expression of the serotonin transporter mRNA and serotonin-containing neurons in the vicinity of the RTN/pFRG of neonatal mice.ConclusionsThese results reveal that the serotonergic system plays a pivotal role in pH homeostasis. Although obtained in vitro in neonatal mice, they suggest that drugs targeting the serotonergic system should be used with caution in infants, pregnant women and breastfeeding mothers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fluoxetine Treatment Abolishes the In Vitro Respiratory Response to Acidosis in Neonatal Mice

Voituron

Shvarev²,

Menuet³

et al. 2010

PLoS ONE

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“…In the last 50 years, tricyclic antidepressants have been the object of intensive research, and numerous results of their action on different receptors, channels and transporters have been reported, although their in vivo pharmacological effects are considered to be mediated almost exclusively by serotonin and norepinephrine reuptake inhibition on SERT and NET [4,6,39]. Detailed structural information about the interaction between drugs and their main targets have been quite scarce, such as the inhibition kinetics data.…”

Section: Discussionmentioning

confidence: 99%

GABA transporter lysine 448: a key residue for tricyclic antidepressants interaction

Cherubino

Miszner

Renna

et al. 2009

Cell. Mol. Life Sci.

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The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (gamma-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially unaffected. The efficacy of desipramine, but not of the other drugs, is strongly increased in the lysine-glutamate or -aspartate mutants K448E and K448D. Comparison of I(max) and K(0.5GABA) in the absence and presence of desipramine showed that both parameters are reduced by the drug in the wild-type and in the K448E mutant. This suggests an uncompetitive inhibition, in which the drug can bind only after the substrate, an explanation in agreement with the lack of effects on the pre-steady-state and leak currents, and with the known structural data.

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The Molecular Basis of the Interaction Between Drugs and Neurotransmitter Transporters

Sitte

Stockner

Freissmuth

2017

Methods and Principles in Medicinal Chemistry

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Structure/Function Relationships in Serotonin Transporter: New Insights from the Structure of a Bacterial Transporter

Cited by 25 publications

References 49 publications

Fluoxetine Treatment Abolishes the In Vitro Respiratory Response to Acidosis in Neonatal Mice

Fluoxetine Treatment Abolishes the In Vitro Respiratory Response to Acidosis in Neonatal Mice

GABA transporter lysine 448: a key residue for tricyclic antidepressants interaction

The Molecular Basis of the Interaction Between Drugs and Neurotransmitter Transporters

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