INT6356

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Context Info
Confidence 0.48
First Reported 1992
Last Reported 2009
Negated 2
Speculated 1
Reported most in Body
Documents 30
Total Number 35
Disease Relevance 4.62
Pain Relevance 9.82

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

signal transduction (Gabbr1) plasma membrane (Gabbr1) transcription factor binding (Gabbr1)
cytoplasm (Gabbr1) signal transducer activity (Gabbr1)
Anatomy Link Frequency
spinal cord 2
tails 2
brain 2
extracellular matrix 2
neurons 1
Gabbr1 (Mus musculus)
Pain Link Frequency Relevance Heat
agonist 550 100.00 Very High Very High Very High
Analgesic 25 100.00 Very High Very High Very High
GABA receptor 17 100.00 Very High Very High Very High
gABA 363 99.98 Very High Very High Very High
Spinal cord 63 99.46 Very High Very High Very High
antagonist 126 98.88 Very High Very High Very High
Pain 132 98.16 Very High Very High Very High
Neuropathic pain 36 97.72 Very High Very High Very High
mu opioid receptor 4 96.72 Very High Very High Very High
antinociception 15 96.64 Very High Very High Very High
Disease Link Frequency Relevance Heat
Nociception 241 98.72 Very High Very High Very High
Pain 160 98.16 Very High Very High Very High
Neuropathic Pain 107 97.72 Very High Very High Very High
Epilepsy 26 96.88 Very High Very High Very High
Cognitive Disorder 48 96.48 Very High Very High Very High
Hyperalgesia 42 94.28 High High
Convulsion 2 93.72 High High
Drug Dependence 57 91.24 High High
Schizophrenia 2 90.48 High High
Depression 27 89.88 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This suggests that the SDs of GABAB1a bind to protein(s) that
localize heteroreceptors at glutamatergic terminals. 
GABAB1a Binding (bind) of
1) Confidence 0.48 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576543 Disease Relevance 0.08 Pain Relevance 0
Therefore, the auxiliary factor binding to SDs of
GABAB1a at the cell surface remains to be identified.
GABAB1a Binding (binding) of
2) Confidence 0.41 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576543 Disease Relevance 0 Pain Relevance 0.25
Based on our understanding of GABAB receptor heteromerization, lack of the GABAB(1) subunit precludes the assembly of functional GABAB receptor [28,36-38].
GABAB Binding (heteromerization) of
3) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2785766 Disease Relevance 0.24 Pain Relevance 0.47
This clearly demonstrates that the lack of heteromeric GABAB(1,2) receptors underlies these phenotypes.
GABAB Binding (underlies) of
4) Confidence 0.37 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15240800 Disease Relevance 0.28 Pain Relevance 0.17
Of importance
for drug discovery, our data also demonstrate that it is possible to
selectively impair GABAB heteroreceptors by targeting their
SDs.



GABAB Binding (heteroreceptors) of
5) Confidence 0.37 Published 2008 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2576543 Disease Relevance 0 Pain Relevance 0.07
In this study, we deleted the primary ligand-binding subunit of metabotropic GABA receptors, GABAB(1), specifically in peripheral nociceptive neurons leaving their expression in the spinal cord and brain intact.
GABAB Binding (binding) of in brain associated with nociception, gaba receptor and spinal cord
6) Confidence 0.36 Published 2009 Journal Mol Pain Section Body Doc Link PMC2785766 Disease Relevance 0.98 Pain Relevance 0.70
In the heteromeric receptor, GABAB(1) is responsible for binding of GABA, whereas GABAB(2) is necessary for surface trafficking and G-protein coupling.
GABAB Binding (binding) of associated with gaba
7) Confidence 0.36 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15240800 Disease Relevance 0 Pain Relevance 0.09
A protein binding to the
first SD of GABAB1a is the extracellular matrix protein fibulin-2,
but whether it mediates GABAB receptor localization is unknown
(19).
GABAB1a Binding (binding) of in extracellular matrix
8) Confidence 0.35 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576543 Disease Relevance 0.07 Pain Relevance 0
We conclude that the pharmacological activity of racemic phenibut relies on R-phenibut and this correlates to the binding affinity of enantiomers of phenibut to the GABAB receptor.
GABAB receptor Binding (affinity) of
9) Confidence 0.35 Published 2008 Journal Eur. J. Pharmacol. Section Abstract Doc Link 18275958 Disease Relevance 0.06 Pain Relevance 0.48
Desensitization of GABAB receptors and antagonism by CGP 35348, prevent bicuculline- and picrotoxin-induced antinociception.
GABAB Binding (Desensitization) of associated with antinociception and analgesic
10) Confidence 0.34 Published 1992 Journal Neuropharmacology Section Title Doc Link 1326728 Disease Relevance 0 Pain Relevance 0.68
The GABAB1 subunit binds the endogenous ligand within its extracellular N-terminus, whilst the GABAB2 subunit is not only essential for the correct trafficking of the GABAB1 subunit to the cell surface, but is also responsible for the interaction of the receptor with its cognate G-protein.
GABAB1 Binding (binds) of
11) Confidence 0.33 Published 2005 Journal CNS Drug Rev Section Abstract Doc Link 16389296 Disease Relevance 0.62 Pain Relevance 0.28
Western blots were performed with lysates of mouse DRG, spinal cord and brain with antibodies recognizing murine GABAB(1) (AB1531, Chemicon) and alpha-tubulin (Sigma Aldrich) according to standard protocols [27].


GABAB Binding (recognizing) of in spinal cord associated with spinal cord
12) Confidence 0.33 Published 2009 Journal Mol Pain Section Body Doc Link PMC2785766 Disease Relevance 0.19 Pain Relevance 0.20
We addressed whether
exogenous application of RSDP to dissociated hippocampal neurons in culture
exerts a dominant-negative effect on heteroreceptors by scavenging a binding
partner of their GABAB1a subunits. 
GABAB1a Binding (binding) of in neurons
13) Confidence 0.31 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576543 Disease Relevance 0 Pain Relevance 0.18
In our experiments, the extracellular matrix protein fibulin-2, which binds to
the first SD of GABAB1a
(19), was without effect on
heteroreceptor function. 
GABAB1a Binding (binds) of in extracellular matrix
14) Confidence 0.31 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576543 Disease Relevance 0 Pain Relevance 0.16
In the absence of agonist, these later compounds may still bind in the GABAB2 HD, but may not lead to the relative movement between the subunits, preventing them from being agonists (Fig. 4).


GABAB2 Neg (not) Binding (bind) of associated with agonist
15) Confidence 0.29 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656813 Disease Relevance 0 Pain Relevance 0.22
The GABAB1 subunit binds the endogenous ligand within its extracellular N-terminus, whilst the GABAB2 subunit is not only essential for the correct trafficking of the GABAB1 subunit to the cell surface, but is also responsible for the interaction of the receptor with its cognate G-protein.
GABAB1 Binding (trafficking) of
16) Confidence 0.25 Published 2005 Journal CNS Drug Rev Section Abstract Doc Link 16389296 Disease Relevance 0.58 Pain Relevance 0.29
Similarly, no alterations were noted in the coupling between GABAB receptor and Gi protein or in the amount of protein.
GABAB receptor Binding (coupling) of
17) Confidence 0.24 Published 1996 Journal Life Sci. Section Abstract Doc Link 8950321 Disease Relevance 0 Pain Relevance 0.58
Indeed, a mutated receptor dimer with two GABAB2 HDs is functional, whereas a mutated receptor with two GABAB1 HDs does not [23].
GABAB1 Binding (receptor) of
18) Confidence 0.22 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656813 Disease Relevance 0 Pain Relevance 0.19
Indeed, the closure of the GABAB1 VFT has been shown to be responsible for GABAB receptor activation [40], and such a closure activates GABAB2 HD whether it is part of the associated subunit (like in the wild-type heterodimer) or linked to the GABAB1 VFT [23].
GABAB1 Binding (linked) of
19) Confidence 0.22 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656813 Disease Relevance 0 Pain Relevance 0.16
COPI binding to the RXR motif of GABAB1 is prevented by GABAB2 thanks to a direct interaction between the intracellular tails of these two subunits through a coiled-coil interaction [8, 10, 54, 61].
GABAB1 Binding (binding) of in tails
20) Confidence 0.22 Published 2007 Journal Current Neuropharmacology Section Body Doc Link PMC2656813 Disease Relevance 0 Pain Relevance 0

General Comments

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