INT221172

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Context Info
Confidence 0.42
First Reported 2008
Last Reported 2009
Negated 2
Speculated 1
Reported most in Body
Documents 32
Total Number 48
Disease Relevance 1.37
Pain Relevance 51.59

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

cytosol (Flna) plasma membrane (Flna) nucleus (Flna)
transcription factor binding (Flna) biological_process (Flna) cytoplasm (Flna)
Anatomy Link Frequency
brain 1
internal 1
Flna (Rattus norvegicus)
Pain Link Frequency Relevance Heat
mu opioid receptor 4560 100.00 Very High Very High Very High
narcan 4528 100.00 Very High Very High Very High
Morphine 2336 99.92 Very High Very High Very High
addiction 720 99.92 Very High Very High Very High
Opioid 2272 99.68 Very High Very High Very High
tolerance 848 99.62 Very High Very High Very High
Analgesic 208 99.08 Very High Very High Very High
opiate 128 98.64 Very High Very High Very High
antagonist 592 98.16 Very High Very High Very High
analgesia 368 97.28 Very High Very High Very High
Disease Link Frequency Relevance Heat
Vibrio Infection 32 97.40 Very High Very High Very High
Skin Cancer 96 97.20 Very High Very High Very High
Drug Dependence 64 85.56 High High
Bordatella Infection 16 82.48 Quite High
Urological Neuroanatomy 32 81.60 Quite High
Neuroblastoma 32 72.72 Quite High
Opiate Addiction 64 39.36 Quite Low
Pain 32 36.32 Quite Low
Decapitation 48 5.00 Very Low Very Low Very Low
Injury 48 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
To confirm that FLNA2561–2565 binds NLX and to deduce the critical amino acid(s) within the NLX interacting FLNA2561–2565 region, we generated 4 alterations of FLNA2561–2565 each with 1 amino acid replaced by alanine (alanine scan).
FLNA2561 Binding (binds) of associated with narcan
1) Confidence 0.42 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.64
It is possible that the ultra-low-dose opioid antagonist attenuation of opioid addictive properties [6], [7] may also be mediated by this high-affinity binding to FLNA.
FLNA Binding (binding) of associated with antagonist and opioid
2) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 1.49
Using FLNA2561–2565 and the alanine-replaced pentapeptides to compete with [3H]NLX binding to FLNA in A7 cell membranes, we show that the lysine residue at FLNA2663 is critical to the NLX–FLNA interaction.
FLNA Binding (binding) of associated with narcan
3) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.62
Additionally, as exogenous GM1 ganglioside has been shown to mimick opioid tolerance in vitro [21] and since blocking GM1 ganglioside via cholera toxin B subunit also blocks the excitatory effects of opiates in vitro [22] and in vivo [23], GM1 ganglioside may also influence MOR–FLNA interactions.
MOR-FLNA Binding (interactions) of associated with mu opioid receptor, tolerance, vibrio infection, opiate and opioid
4) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.10 Pain Relevance 1.15
To confirm that NLX binding to FLNA prevents the chronic morphine-induced Gi/o-to-Gs coupling switch, we utilized organotypic rat brain striatal slice cultures.
FLNA Binding (binding) of in brain associated with narcan and morphine
5) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.08 Pain Relevance 1.11
These data together suggest that NLX binds with high affinity to FLNA with the binding site located at FLNA2561–2565.


FLNA Binding (binds) of associated with narcan
6) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.66
To assess the functional significance of this high-affinity interaction, we used peptide fragments containing the binding site to prevent NLX from binding full-length FLNA in organotypic striatal slice cultures.
FLNA Binding (binding) of associated with narcan
7) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 1.14
NLX binds FLNA tightly with critical involvement of a 5-amino acid segment that is intracellular but near its c-terminal transmembrane domain.
FLNA Binding (binds) of associated with narcan
8) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 1.39
The notion that NLX binds to the extreme carboxyl terminus of FLNA that tethers to the internal potion of cell membranes is supported by our data illustrating that FLNA2561–2565 (VAKGL) prevented the [3H]- and FITC-NLX labeling that localized internally in intact A7 but not M2 cells (Fig. 6).
FLNA Binding (binds) of in internal associated with narcan
9) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.78
NLX binding to FLNA-expressing cells
FLNA Binding (binding) of associated with narcan
10) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.09 Pain Relevance 0.39
We deduced the precise binding site on FLNA by using overlapping peptides within the c-terminal, since c-terminal FLNA was shown to interact with MOR using a yeast-two hybrid [15].
FLNA Binding (interact) of associated with mu opioid receptor
11) Confidence 0.32 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.99
Using FLNA2561–2565 and the alanine-replaced pentapeptides to compete with [3H]NLX binding to FLNA in A7 cell membranes, we show that the lysine residue at FLNA2663 is critical to the NLX–FLNA interaction.
FLNA2561 Binding (binding) of associated with narcan
12) Confidence 0.32 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.63
The demonstration that both purified MOR and FLNA proteins bind to VAKGL suggests that the VAKGL pentapeptide can similarly prevent the MOR–FLNA interaction but by binding to either protein.
FLNA Binding (bind) of associated with mu opioid receptor
13) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2628740 Disease Relevance 0 Pain Relevance 1.09
NLX binding in FLNA-expressing cells and affinity measurement
FLNA Binding (binding) of associated with narcan
14) Confidence 0.29 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.15 Pain Relevance 0.94
To deduce the precise binding domain within FLNA where NLX binds, several overlapping peptide sequences derived from the carboxy-terminus where FLNA intersects with synaptic membranes were used to absorb [3H]NLX.
FLNA Binding (intersects) of associated with narcan
15) Confidence 0.29 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.06 Pain Relevance 0.64
This prior study by Onoprishvili et al., the first to show that FLNA interacts with the c-terminal of MOR, proposed a role for FLNA in receptor regulation and trafficking [15].
FLNA Binding (interacts) of associated with mu opioid receptor
16) Confidence 0.29 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.08 Pain Relevance 1.09
Using FLNA2561–2565 and the alanine-replaced pentapeptides to compete with [3H]NLX binding to FLNA in A7 cell membranes, we show that the lysine residue at FLNA2663 is critical to the NLX–FLNA interaction.
FLNA Binding (interaction) of associated with narcan
17) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.63
By binding to FLNA, NLX could block this particular MOR–FLNA interaction and stabilize the MOR-FLNA-G protein complexes, thereby reducing the morphine-induced release of MORs and their subsequent coupling with Gs in response to receptor stimulation.
MOR-FLNA Binding (interaction) of associated with mu opioid receptor, narcan and morphine
18) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.06 Pain Relevance 1.43
By binding to FLNA, NLX and its analogs prevent this altered MOR–FLNA interaction, thereby preventing the release from the complexes and the resultant altered coupling.
MOR-FLNA Neg (prevent) Binding (interaction) of associated with mu opioid receptor and narcan
19) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0.07 Pain Relevance 1.83
To confirm that FLNA2561–2565 binds NLX and to deduce the critical amino acid(s) within the NLX interacting FLNA2561–2565 region, we generated 4 alterations of FLNA2561–2565 each with 1 amino acid replaced by alanine (alanine scan).
FLNA2561 Binding (binds) of associated with narcan
20) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2212716 Disease Relevance 0 Pain Relevance 0.67

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