INT15092

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Context Info
Confidence 0.67
First Reported 1991
Last Reported 2010
Negated 0
Speculated 2
Reported most in Abstract
Documents 17
Total Number 19
Disease Relevance 7.32
Pain Relevance 6.70

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (SLC6A4) endosome (SLC6A4) plasma membrane (SLC6A4)
Anatomy Link Frequency
oocytes 3
MEG-01 2
synapse 2
Caco-2 1
SLC6A4 (Homo sapiens)
Pain Link Frequency Relevance Heat
Serotonin 62 100.00 Very High Very High Very High
monoamine 46 99.92 Very High Very High Very High
Neurotransmitter 41 99.24 Very High Very High Very High
Migraine 16 97.64 Very High Very High Very High
Pain 189 96.64 Very High Very High Very High
fluoxetine 17 96.60 Very High Very High Very High
antagonist 2 94.38 High High
5HT 8 93.24 High High
Fibrositis 94 92.48 High High
Desipramine 3 89.28 High High
Disease Link Frequency Relevance Heat
Blister 2 99.58 Very High Very High Very High
Chronic Fatigue Syndrome 11 99.38 Very High Very High Very High
Vibrio Infection 18 99.34 Very High Very High Very High
Headache 8 97.64 Very High Very High Very High
Syndrome 14 97.60 Very High Very High Very High
Migraine Without Aura 14 94.36 High High
Migraine With Aura 16 92.84 High High
Fibromyalgia 94 92.48 High High
Traumatic Stress Disorders 5 91.00 High High
Pain 198 88.80 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The compositional alteration was associated with up-regulation and down-regulation of 5HT2BR and 5HTT genes, respectively.
Positive_regulation (up-regulation) of 5HTT
1) Confidence 0.67 Published 2008 Journal Exp. Toxicol. Pathol. Section Abstract Doc Link 18511249 Disease Relevance 0.28 Pain Relevance 0.39
A short-term exposure of the cells to a high concentration of glucose decreases the activity of the transporter, whereas a longer exposure of the cells to a high concentration of glucose increases the activity of SERT, without interfering with its affinity.
Positive_regulation (increases) of SERT
2) Confidence 0.61 Published 2008 Journal Nutr Neurosci Section Abstract Doc Link 19000377 Disease Relevance 0 Pain Relevance 0.28
Results revealed that SERT is present in control-untreated MEG-01 cells. beta-TPA-differentiating MEG-01 cells showed a redistribution of SERT fluorescence, diffuse to cell bodies and blebs along with a 3-fold SERT mRNA increase and a moderate raise in SERT protein (1.5/1.4-fold) by immunoblot and re-uptake assays.
Positive_regulation (increase) of SERT in MEG-01 associated with blister
3) Confidence 0.61 Published 2010 Journal Neurochem. Res. Section Abstract Doc Link 20041293 Disease Relevance 0.31 Pain Relevance 0.14
The SERT activity levels in Caco-2 cells increased in correlation with the onset and maintenance of the morphological and functional differentiation of the cells.
Positive_regulation (increased) of SERT in Caco-2
4) Confidence 0.50 Published 2006 Journal J. Physiol. Pharmacol. Section Abstract Doc Link 16601320 Disease Relevance 0.17 Pain Relevance 0.19
Fluoxetine significantly prolonged the time constant for 5-HT-induced hSERT current.
Positive_regulation (5-HT-induced) of hSERT
5) Confidence 0.49 Published 2006 Journal Acta Pharmacol. Sin. Section Body Doc Link 16490163 Disease Relevance 0 Pain Relevance 0
Allelic variation of the human serotonin transporter gene (HSERT), a highly plausible candidate gene for susceptibility to migraine, was investigated in 266 individuals with migraine, including 173 having migraine without aura (MO), 94 having migraine with aura (MA), 18 with co-occurrence of MO and MA, plus 133 unaffected controls.
Spec (investigated) Positive_regulation (variation) of HSERT associated with migraine with aura, migraine, migraine without aura and serotonin
6) Confidence 0.49 Published 1998 Journal Cephalalgia Section Abstract Doc Link 9601620 Disease Relevance 1.02 Pain Relevance 0.62
Treatment with SB224289 (selective antagonist of 5-HT1B), fluoxetine (SERT inhibitor), SERT RNA-interference, and iproniazid (monoamine oxidase-A inhibitor), blocked 5-HT-induced S100A4/Mts1. 5-HT signaling mediated phosphorylation (p) of extracellular signal-regulated kinase 1/2 (pERK1/2), but pERK1/2 nuclear translocation depended on SERT, monoamine oxidase activity, and reactive oxygen species.
Positive_regulation (depended) of SERT associated with antagonist, monoamine and fluoxetine
7) Confidence 0.47 Published 2005 Journal Circ. Res. Section Abstract Doc Link 16002749 Disease Relevance 0.27 Pain Relevance 0.34
Since the re-uptake of monoamine neurotransmitters through specific transporters is the major method of elimination from the neural synapse, it is not surprising that the genetic variations in norepinephrine transporter gene (SLC6A2) and the serotonin transporter gene (SLC6A4) affect monoamine neurotransmitter mediated human behaviors including responses to painful stimuli.
Positive_regulation (variations) of serotonin transporter in synapse associated with pain, neurotransmitter, serotonin and monoamine
8) Confidence 0.47 Published 2006 Journal Mol Pain Section Body Doc Link PMC1543620 Disease Relevance 0.50 Pain Relevance 0.98
Since the re-uptake of monoamine neurotransmitters through specific transporters is the major method of elimination from the neural synapse, it is not surprising that the genetic variations in norepinephrine transporter gene (SLC6A2) and the serotonin transporter gene (SLC6A4) affect monoamine neurotransmitter mediated human behaviors including responses to painful stimuli.
Positive_regulation (variations) of SLC6A4 in synapse associated with pain, neurotransmitter, serotonin and monoamine
9) Confidence 0.47 Published 2006 Journal Mol Pain Section Body Doc Link PMC1543620 Disease Relevance 0.50 Pain Relevance 0.99
METHODS: A heterologous expression system was used to introduce human serotonin transporter (hSERT) into Xenopus oocytes.
Positive_regulation (introduce) of hSERT in oocytes
10) Confidence 0.46 Published 2006 Journal Acta Pharmacol. Sin. Section Body Doc Link 16490163 Disease Relevance 0 Pain Relevance 0
The 5-HT-induced hSERT currents were dose-dependently reversed by fluoxetine.
Positive_regulation (5-HT-induced) of hSERT
11) Confidence 0.43 Published 2006 Journal Acta Pharmacol. Sin. Section Body Doc Link 16490163 Disease Relevance 0 Pain Relevance 0
Results revealed that SERT is present in control-untreated MEG-01 cells. beta-TPA-differentiating MEG-01 cells showed a redistribution of SERT fluorescence, diffuse to cell bodies and blebs along with a 3-fold SERT mRNA increase and a moderate raise in SERT protein (1.5/1.4-fold) by immunoblot and re-uptake assays.
Positive_regulation (increase) of SERT protein in MEG-01 associated with blister
12) Confidence 0.41 Published 2010 Journal Neurochem. Res. Section Abstract Doc Link 20041293 Disease Relevance 0.31 Pain Relevance 0.14
Analysis of six hSERT/bSERT chimeras and subsequent species-scanning mutagenesis of each isoform revealed methionine-180, tyrosine-495, and phenylalanine-513 to be responsible for the increase in citalopram and paroxetine potencies at hSERT and methionine-180 and phenylalanine-513 to confer species selectivity at hSERT for fluoxetine and imipramine.
Positive_regulation (increase) of hSERT associated with fluoxetine
13) Confidence 0.41 Published 2001 Journal J. Neurochem. Section Abstract Doc Link 11677251 Disease Relevance 0 Pain Relevance 0.64
RESULTS: hSERT-expressing oocytes were perfused with 10 micromol/L serotonin (5-HT) to induce hSERT-current.
Positive_regulation (induce) of hSERT in oocytes
14) Confidence 0.40 Published 2006 Journal Acta Pharmacol. Sin. Section Body Doc Link 16490163 Disease Relevance 0 Pain Relevance 0
METHODS: A heterologous expression system was used to introduce human serotonin transporter (hSERT) into Xenopus oocytes.
Positive_regulation (introduce) of serotonin transporter in oocytes
15) Confidence 0.40 Published 2006 Journal Acta Pharmacol. Sin. Section Body Doc Link 16490163 Disease Relevance 0 Pain Relevance 0
The activity of the serotonin transporter in this cell line is stimulated in response to overnight (16-h) incubation with increasing concentrations of cholera toxin (0.1-1,000 ng/ml).
Positive_regulation (stimulated) of serotonin transporter associated with vibrio infection and serotonin
16) Confidence 0.14 Published 1991 Journal J. Biol. Chem. Section Abstract Doc Link 1714897 Disease Relevance 0.54 Pain Relevance 0.36
Isobutylmethylxanthine (100 microM), dibutyryl cAMP (100 microM), and forskolin (100 microM) mimic the action of cholera toxin, eliciting a 1.6-2.5-fold stimulation of the serotonin transporter activity.
Positive_regulation (stimulation) of serotonin transporter associated with vibrio infection and serotonin
17) Confidence 0.14 Published 1991 Journal J. Biol. Chem. Section Abstract Doc Link 1714897 Disease Relevance 0.87 Pain Relevance 0.35
A study conducted in 78 CFS patients showed a significant increase of longer allelic variants of the serotonin transporter (5-HTT) gene promoter polymorphism, which affects the transcriptional efficiency of 5-HTT [35].
Positive_regulation (increase) of serotonin transporter associated with chronic fatigue syndrome and serotonin
18) Confidence 0.08 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779444 Disease Relevance 1.54 Pain Relevance 0.65
Allelic variation of the human serotonin transporter gene (HSERT), a highly plausible candidate gene for susceptibility to migraine, was investigated in 266 individuals with migraine, including 173 having migraine without aura (MO), 94 having migraine with aura (MA), 18 with co-occurrence of MO and MA, plus 133 unaffected controls.
Spec (investigated) Positive_regulation (variation) of serotonin transporter gene associated with migraine with aura, migraine, migraine without aura and serotonin
19) Confidence 0.08 Published 1998 Journal Cephalalgia Section Abstract Doc Link 9601620 Disease Relevance 1.02 Pain Relevance 0.62

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