INT97984

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Context Info
Confidence 0.59
First Reported 1999
Last Reported 2011
Negated 0
Speculated 5
Reported most in Abstract
Documents 45
Total Number 52
Disease Relevance 15.43
Pain Relevance 18.09

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
platelets 3
BeWo 2
gut 2
SK-N-MC 2
cingulate cortex 1
SLC6A4 (Homo sapiens)
Pain Link Frequency Relevance Heat
Serotonin 321 100.00 Very High Very High Very High
cytokine 4 99.98 Very High Very High Very High
fluoxetine 77 99.92 Very High Very High Very High
sSRI 198 99.82 Very High Very High Very High
Inflammation 16 99.78 Very High Very High Very High
Duloxetine 7 99.70 Very High Very High Very High
depression 104 99.50 Very High Very High Very High
Calcitonin gene-related peptide 7 99.46 Very High Very High Very High
Desipramine 2 99.28 Very High Very High Very High
substance P 12 99.24 Very High Very High Very High
Disease Link Frequency Relevance Heat
Increased Venous Pressure Under Development 6 99.92 Very High Very High Very High
Infection 3 99.92 Very High Very High Very High
INFLAMMATION 12 99.78 Very High Very High Very High
Depression 130 99.50 Very High Very High Very High
Hypertension 9 99.48 Very High Very High Very High
Pigment Disorder 96 99.36 Very High Very High Very High
Cardiovascular Disease 9 99.36 Very High Very High Very High
Irritable Bowel Syndrome /

Irritable Bowel Syndrome Super

11 99.08 Very High Very High Very High
Congenital Anomalies 15 98.96 Very High Very High Very High
Functional Bowel Disorder 17 98.28 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Among the compounds identified were several previously reported inhibitors of the hSERT, as well as compounds having structural similarity to the tricyclic antidepressant drugs.
Negative_regulation (inhibitors) of hSERT associated with tricyclic antidepressant
1) Confidence 0.59 Published 2006 Journal J Biomol Screen Section Abstract Doc Link 17099247 Disease Relevance 0 Pain Relevance 0.47
BACKGROUND: It is unclear whether decreased serotonin transporter function contributes to sensorimotor abnormalities in irritable bowel syndrome.
Spec (whether) Negative_regulation (decreased) of serotonin transporter in bowel associated with congenital anomalies, spastic colon and serotonin
2) Confidence 0.59 Published 2006 Journal Aliment. Pharmacol. Ther. Section Abstract Doc Link 16393306 Disease Relevance 0.20 Pain Relevance 0.19
CONCLUSIONS: Acute serotonin transporter inhibition in man increases colonic phasic contractility and the occurrence of high-amplitude propagated contractions, increases colonic compliance and suppresses the colonic tonic response to a meal.
Negative_regulation (inhibition) of serotonin transporter
3) Confidence 0.59 Published 2006 Journal Aliment. Pharmacol. Ther. Section Body Doc Link 16393306 Disease Relevance 0 Pain Relevance 0
Loss of serotonin (5-hydroxytryptamine [5-HT]) receptors or of the serotonin transporter (SERT) attenuates pulmonary hypertension in animals, and polymorphisms causing gain of SERT function are linked to clinical pulmonary vascular disease.
Negative_regulation (Loss) of SERT associated with hypertension, increased venous pressure under development and serotonin
4) Confidence 0.55 Published 2005 Journal Circ. Res. Section Abstract Doc Link 16002749 Disease Relevance 0.37 Pain Relevance 0.14
Loss of serotonin (5-hydroxytryptamine [5-HT]) receptors or of the serotonin transporter (SERT) attenuates pulmonary hypertension in animals, and polymorphisms causing gain of SERT function are linked to clinical pulmonary vascular disease.
Negative_regulation (Loss) of serotonin transporter associated with hypertension, increased venous pressure under development and serotonin
5) Confidence 0.55 Published 2005 Journal Circ. Res. Section Abstract Doc Link 16002749 Disease Relevance 0.37 Pain Relevance 0.14
Uptake of (3)H-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) Na(+)-dependent and Cl(-)-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine.
Negative_regulation (inhibitors) of hSERT in BeWo associated with desipramine, serotonin, fluoxetine and clonidine
6) Confidence 0.55 Published 2006 Journal J. Biochem. Mol. Biol. Section Abstract Doc Link 16889681 Disease Relevance 0 Pain Relevance 0.35
Uptake of (3)H-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) Na(+)-dependent and Cl(-)-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine.
Negative_regulation (inhibitors) of serotonin plasmalemmal transporter in BeWo associated with desipramine, serotonin, fluoxetine and clonidine
7) Confidence 0.55 Published 2006 Journal J. Biochem. Mol. Biol. Section Abstract Doc Link 16889681 Disease Relevance 0 Pain Relevance 0.35
Individuals carrying an s-allele have a reduced 5-HTT activity and therefore a compensatory decrease in 5-HT1 activity would be expected [39].
Negative_regulation (reduced) of 5-HTT
8) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2717925 Disease Relevance 0.45 Pain Relevance 1.42
Fluoxetine, a SERT inhibitor, was a more potent inhibitor of uptake (IC50 0.05 microM) than d-fenfluramine, but the anorectic agent, phentermine, had no effect.
Negative_regulation (inhibitor) of SERT associated with appetite loss and fluoxetine
9) Confidence 0.51 Published 2003 Journal J. Thromb. Haemost. Section Abstract Doc Link 14675103 Disease Relevance 0.42 Pain Relevance 0.27
Therefore, the aim of the present study was to investigate whether tegaserod inhibits SERT-, DAT-, and NET-mediated transport.
Spec (whether) Negative_regulation (inhibits) of SERT
10) Confidence 0.50 Published 2007 Journal Digestion Section Abstract Doc Link 17510552 Disease Relevance 0.16 Pain Relevance 0.30
By inhibiting SERT and increasing local 5-HT concentrations in the gut wall, tegaserod might exert its prokinetic action via a synergism between 5-HT4 agonism and low-affinity SERT inhibition.


Negative_regulation (inhibition) of SERT in gut
11) Confidence 0.50 Published 2007 Journal Digestion Section Body Doc Link 17510552 Disease Relevance 0 Pain Relevance 0
Tegaserod inhibits the serotonin transporter SERT.
Negative_regulation (inhibits) of serotonin transporter associated with serotonin
12) Confidence 0.50 Published 2007 Journal Digestion Section Title Doc Link 17510552 Disease Relevance 0.19 Pain Relevance 0.32
By inhibiting SERT and increasing local 5-HT concentrations in the gut wall, tegaserod might exert its prokinetic action via a synergism between 5-HT4 agonism and low-affinity SERT inhibition.


Negative_regulation (inhibiting) of SERT in gut
13) Confidence 0.50 Published 2007 Journal Digestion Section Body Doc Link 17510552 Disease Relevance 0 Pain Relevance 0
However, after 3-day incubation, both TNF-alpha and IFN-gamma elicited significant decreases in SERT function.
Negative_regulation (decreases) of SERT
14) Confidence 0.48 Published 2007 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 17170025 Disease Relevance 0.25 Pain Relevance 0.36
These two cytokines also induced decreases in SERT mRNA and protein levels.
Negative_regulation (decreases) of SERT mRNA associated with cytokine
15) Confidence 0.48 Published 2007 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 17170025 Disease Relevance 0.23 Pain Relevance 0.33
RESULTS: Both escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter (K(i) = 1.1 and 1.4 nmol/L, respectively).
Negative_regulation (inhibitors) of serotonin transporter
16) Confidence 0.47 Published 2001 Journal Biol. Psychiatry Section Body Doc Link 11543737 Disease Relevance 0 Pain Relevance 0
Although several antidepressants (including fluoxetine, imipramine, citalopram, venlafaxine, and duloxetine) are known to inhibit the serotonin transporter (SERT), whether or not these molecules compete with 5-hydroxytryptamine (serotonin) (5-HT) for binding to SERT has remained controversial.
Spec (whether) Negative_regulation (inhibit) of SERT associated with antidepressant, serotonin, duloxetine and fluoxetine
17) Confidence 0.43 Published 2008 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 18801947 Disease Relevance 0 Pain Relevance 0.37
Although several antidepressants (including fluoxetine, imipramine, citalopram, venlafaxine, and duloxetine) are known to inhibit the serotonin transporter (SERT), whether or not these molecules compete with 5-hydroxytryptamine (serotonin) (5-HT) for binding to SERT has remained controversial.
Spec (whether) Negative_regulation (inhibit) of serotonin transporter associated with antidepressant, serotonin, duloxetine and fluoxetine
18) Confidence 0.43 Published 2008 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 18801947 Disease Relevance 0 Pain Relevance 0.37
Incubation of MDMA treated cells with the SERT inhibitor, fluoxetine (500 nM) or the MAO-B inhibitor, L-deprenyl (0.1 mM) for 30 min prior to DA, significantly blocked free radical production and cell death.
Negative_regulation (inhibitor) of SERT associated with dopamine, death and fluoxetine
19) Confidence 0.43 Published 2004 Journal Neurosci. Lett. Section Abstract Doc Link 15308297 Disease Relevance 0.26 Pain Relevance 0.54
In addition, SERT activity was inhibited by the intracellular modulators protein kinase C and cAMP, either after short or long-term treatment.
Negative_regulation (inhibited) of SERT associated with kinase c
20) Confidence 0.43 Published 2006 Journal J. Physiol. Pharmacol. Section Abstract Doc Link 16601320 Disease Relevance 0.14 Pain Relevance 0.22

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