INT61825

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Context Info
Confidence 0.59
First Reported 1995
Last Reported 2010
Negated 2
Speculated 0
Reported most in Body
Documents 47
Total Number 48
Disease Relevance 6.52
Pain Relevance 21.27

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

aging (Slc6a3) plasma membrane (Slc6a3) transmembrane transport (Slc6a3)
Anatomy Link Frequency
striatum 5
plasma 2
brain 2
prefrontal 2
synapse 2
Slc6a3 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Dopamine 2242 100.00 Very High Very High Very High
cocaine 242 99.84 Very High Very High Very High
Enkephalin 23 99.78 Very High Very High Very High
Kinase C 53 99.40 Very High Very High Very High
imagery 79 99.22 Very High Very High Very High
anesthesia 26 98.72 Very High Very High Very High
Nucleus accumbens 139 98.56 Very High Very High Very High
fortral 6 98.18 Very High Very High Very High
halothane 16 98.16 Very High Very High Very High
Serotonin 76 97.72 Very High Very High Very High
Disease Link Frequency Relevance Heat
Drug Induced Neurotoxicity 1 99.92 Very High Very High Very High
Disease 153 99.38 Very High Very High Very High
Urological Neuroanatomy 15 99.14 Very High Very High Very High
Gliosis 20 98.76 Very High Very High Very High
Targeted Disruption 14 97.98 Very High Very High Very High
Attention Deficit Hyperactivity Disorder 832 96.74 Very High Very High Very High
Diabetes Mellitus 39 94.28 High High
Natriuresis 1 92.84 High High
Cognitive Disorder 109 89.36 High High
Parkinson's Disease 112 87.04 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The results demonstrate that decreased DA transporter function in aged rats masks age-related differences in K(+)-evoked striatal DA release when microdialysis methods are used, resulting in net equalization of K(+)-evoked striatal DA overflow in young versus aged F344 rats.
Negative_regulation (decreased) of DA transporter
1) Confidence 0.59 Published 2001 Journal Neurobiol. Aging Section Abstract Doc Link 11378257 Disease Relevance 0 Pain Relevance 0
However, as found previously in DOCA-treated rats, there were increased enkephalin (ENK)-mRNA and decreased dopamine transporter (DAT) binding levels throughout the striatum in Lasix+salt and decreased ENK-mRNA in Lasixnosalt rats versus Vehicle.
Negative_regulation (decreased) of DAT in striatum associated with dopamine and enkephalin
2) Confidence 0.58 Published 2003 Journal Neuroendocrinology Section Abstract Doc Link 12845226 Disease Relevance 0.05 Pain Relevance 0.58
However, as found previously in DOCA-treated rats, there were increased enkephalin (ENK)-mRNA and decreased dopamine transporter (DAT) binding levels throughout the striatum in Lasix+salt and decreased ENK-mRNA in Lasixnosalt rats versus Vehicle.
Negative_regulation (decreased) of dopamine transporter in striatum associated with dopamine and enkephalin
3) Confidence 0.58 Published 2003 Journal Neuroendocrinology Section Abstract Doc Link 12845226 Disease Relevance 0.05 Pain Relevance 0.58
The drug has been shown to block the dopamine transporter (DAT) and thereby elevates extracellular dopamine (DA) levels in the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), which are brain areas of the mesocorticolimbic DA system involved in the locomotor and reinforcing effects of psychostimulants and other drugs of abuse [7-13].
Negative_regulation (block) of DAT in prefrontal associated with nucleus accumbens, ventral tegmentum and dopamine
4) Confidence 0.57 Published 2006 Journal Behav Brain Funct Section Body Doc Link PMC1360669 Disease Relevance 0.29 Pain Relevance 0.65
This phosphorylation/dephosphorylation status is closely coupled to DAT endocytic trafficking and interestingly PKC activation has been shown to decrease DAT activity through clathrin-mediated endocytosis [31,55], an event associated with an increase in DAT phosphorylation [52].
Negative_regulation (decrease) of DAT associated with kinase c
5) Confidence 0.48 Published 2009 Journal Mol Brain Section Body Doc Link PMC2687442 Disease Relevance 0 Pain Relevance 0.20
GBR 12909 and nomifensine, inhibitors of DAT, decreased the release of [(3)H]DA evoked by halothane.
Negative_regulation (inhibitors) of DAT associated with dopamine and halothane
6) Confidence 0.42 Published 2007 Journal Cell. Mol. Neurobiol. Section Abstract Doc Link 17680357 Disease Relevance 0 Pain Relevance 1.16
On this view, cocaine, which blocks the dopamine transporter (DAT) and thus elevates extracellular dopamine levels, reduces the strength of the stimulus required to produce a rewarding effect of a given intensity (an action analogous to lowering the KM of an enzyme).
Negative_regulation (blocks) of DAT associated with dopamine and cocaine
7) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2994896 Disease Relevance 0 Pain Relevance 0.27
These data suggest that under hypoinsulinemic conditions, in which PI3K signaling is diminished, the ability of AMPH to cause DA efflux is impaired, possibly by decreasing DAT function.


Negative_regulation (decreasing) of DAT associated with dopamine
8) Confidence 0.41 Published 2007 Journal PLoS Biology Section Body Doc Link PMC2020502 Disease Relevance 0 Pain Relevance 0.60
Thus, the current findings suggest that a reduction in insulin signaling leads to a decrease in DAT function, a notion supported by the previous study from Owens et al. [14] showing that AMPH-naive, STZ-treated rats exhibit significantly less DA uptake in striatum as determined in vivo with HSCA and ex vivo in synaptosomes.
Negative_regulation (decrease) of DAT in striatum associated with dopamine
9) Confidence 0.41 Published 2007 Journal PLoS Biology Section Body Doc Link PMC2020502 Disease Relevance 0 Pain Relevance 0.57
These findings, together with our electrochemical data (Figures 2 and 3), support the hypothesis that the reduction in AMPH-induced DA efflux caused by STZ treatment is a consequence of a reduction in DAT levels on the plasma membrane and are consistent with the previously reported blunted behavioral properties of AMPH under hypoinsulinemic conditions [12,33,34,51].


Negative_regulation (reduction) of DAT in plasma associated with dopamine
10) Confidence 0.36 Published 2007 Journal PLoS Biology Section Body Doc Link PMC2020502 Disease Relevance 0 Pain Relevance 0.22
When the DAT is blocked in the presence of a low therapeutic MPH dose, the resting level of extracellular dopamine rises by about 6-fold.
Negative_regulation (blocked) of DAT associated with dopamine
11) Confidence 0.34 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2701285 Disease Relevance 0 Pain Relevance 0.68
NGF-enhanced DAT activity was inhibited to a similar extent as the basal levels.
Negative_regulation (inhibited) of DAT
12) Confidence 0.33 Published 2006 Journal J Mol Signal Section Body Doc Link PMC1769494 Disease Relevance 0 Pain Relevance 0.19
In contrast, in vitro inhibition of either PI3K or Akt causes a decrease in DA uptake capacity and a redistribution of DAT away from the plasma membrane [11,13].
Negative_regulation (redistribution) of DAT in plasma associated with dopamine
13) Confidence 0.30 Published 2007 Journal PLoS Biology Section Body Doc Link PMC2020502 Disease Relevance 0.06 Pain Relevance 0.34
None of these anesthetics was predicted to inhibit DAT at concentrations that produce anesthesia.
Negative_regulation (inhibit) of DAT associated with anesthesia
14) Confidence 0.29 Published 2002 Journal Anesth. Analg. Section Abstract Doc Link 12351264 Disease Relevance 0 Pain Relevance 0.48
Rat DAT was inhibited in a dose-dependent fashion by propofol (IC(50) = 120 micro M), etomidate (IC(50) = 100 micro M), and ketamine (IC(50) = 210 micro M), but not by pentobarbital.
Negative_regulation (inhibited) of DAT associated with ketamine
15) Confidence 0.29 Published 2002 Journal Anesth. Analg. Section Abstract Doc Link 12351264 Disease Relevance 0 Pain Relevance 0.47
Cocaine inhibited N-methyl-D-aspartate-stimulated [3H]dopamine release in a concentration-dependent manner with a Ki of approximately 10 microM, under conditions in which the dopamine transporter (DAT) was blocked by 10 microM nomifensine.
Negative_regulation (blocked) of DAT associated with dopamine and cocaine
16) Confidence 0.29 Published 2006 Journal Eur. J. Pharmacol. Section Abstract Doc Link 16480713 Disease Relevance 0 Pain Relevance 0.63
The second hypothesis suggests that increased extracellular dopamine subsequent to DAT blockade overcomes the inhibitory effects for activation of the presynaptic autoreceptors, leading to a net effect of dopamine accumulation in the synapse and subsequent amplification of dopamine signals [56].
Negative_regulation (blockade) of DAT in synapse associated with dopamine
17) Confidence 0.29 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2701285 Disease Relevance 0.08 Pain Relevance 0.38
Seeman and Madras [42, 43] suggest that the therapeutical relevance of subcortical DAT blockade by MPH is based on the drug’s biphasic action.
Negative_regulation (blockade) of DAT
18) Confidence 0.28 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2701285 Disease Relevance 0.06 Pain Relevance 0.47
Volkow and colleagues [56] suggest that the therapeutical relevance of subcortical DAT blockade by MPH is based on two mechanisms.
Negative_regulation (blockade) of DAT
19) Confidence 0.28 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2701285 Disease Relevance 0.15 Pain Relevance 0.55
As shown in Figure 4, chronic depletion of insulin results in a significant (>40%) decrease in the level of biotinylated, membrane-associated DAT within synaptosomes, indicating that DAT cell surface expression was significantly reduced in hypoinsulinemic rats.
Negative_regulation (decrease) of DAT
20) Confidence 0.26 Published 2007 Journal PLoS Biology Section Body Doc Link PMC2020502 Disease Relevance 0 Pain Relevance 0.20

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