INT89184

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Context Info
Confidence 0.77
First Reported 2000
Last Reported 2010
Negated 1
Speculated 1
Reported most in Body
Documents 55
Total Number 64
Disease Relevance 23.85
Pain Relevance 10.65

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 (Mc4r) plasma membrane (Mc4r) signal transducer activity (Mc4r)
Anatomy Link Frequency
neurons 6
brain 5
fat 4
hypothalamus 3
body 3
Mc4r (Mus musculus)
Mc4r - L106P (1)
Pain Link Frequency Relevance Heat
agonist 564 100.00 Very High Very High Very High
antagonist 277 100.00 Very High Very High Very High
melanocortin 1 receptor 239 100.00 Very High Very High Very High
cocaine 62 100.00 Very High Very High Very High
Central nervous system 336 99.08 Very High Very High Very High
Lasting pain 3 99.04 Very High Very High Very High
medulla 544 98.68 Very High Very High Very High
amygdala 160 98.60 Very High Very High Very High
Inflammation 108 98.60 Very High Very High Very High
Spinal cord 12 98.60 Very High Very High Very High
Disease Link Frequency Relevance Heat
Obesity 1570 99.80 Very High Very High Very High
Neuropathic Pain 66 99.64 Very High Very High Very High
Sprains And Strains 190 99.52 Very High Very High Very High
Pain 74 99.04 Very High Very High Very High
Hyperphagia 97 98.62 Very High Very High Very High
INFLAMMATION 110 98.60 Very High Very High Very High
Appetite Loss 382 98.48 Very High Very High Very High
Body Weight 300 97.92 Very High Very High Very High
Hyperinsulinism 23 97.90 Very High Very High Very High
Chronic Disease 17 97.28 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The key findings included 1) that the coat color phenotype in the lethal yellow (A(Y)/a) mouse is due to antagonism of the melanocortin-1 receptor (MC1R) by the agouti gene product; 2) the MC3R and MC4R are expressed in CNS centers involved in energy homeostasis, and 3) the combined results of pharmacological studies showing that agouti is an antagonist of the MC4R and transgenic studies showing that inhibition or loss of the MC4R recapitulate the lethal yellow phenotype.
Gene_expression (expressed) of MC4R associated with targeted disruption, melanocortin 1 receptor and antagonist
1) Confidence 0.77 Published 2002 Journal Neuropeptides Section Abstract Doc Link 12359499 Disease Relevance 0.31 Pain Relevance 0.15
[121] This could explain the extensive expression of mc3r and mc4r, despite the very limited POMC axonal presence in the VMH.
Gene_expression (expression) of mc4r
2) Confidence 0.76 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.21 Pain Relevance 0.11
This shows sensitivity to quantitative variation in MC4R expression [97,100], with mechanisms such as poor cell-surface expression or intracellular retention of the mutant receptors [101,102].
Gene_expression (expression) of MC4R
3) Confidence 0.76 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.71 Pain Relevance 0.14
MC4R alone is expressed in the SON and MC4R ko mice are particularly prone to gaining weight on a high fat diet, even when compared with ob/ob mice [165].
Gene_expression (expressed) of MC4R in fat associated with obesity
4) Confidence 0.76 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.10 Pain Relevance 0.09
To identify which sites of mc4r expression are most relevant for mediating these effects, mice were generated with a loxP-modified, null mc4r allele (loxTB mc4r) that can be reactivated by Cre-recombinase [139].
Gene_expression (expression) of mc4r
5) Confidence 0.76 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.39 Pain Relevance 0.30
Restoration of normal mc4r expression in the PVN and a subpopulation of amygdala neurones, using sim1-Cre transgenic mice, prevented 60% of the obesity [139].
Gene_expression (expression) of mc4r in amygdala associated with targeted disruption, obesity and amygdala
6) Confidence 0.76 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.44 Pain Relevance 0.23
In contrast to the restricted distribution of the POMC neurones, MC4R and MC3R are widely present throughout the brain, although with different patterns of distribution (Table 3).
Gene_expression (present) of MC4R in brain
7) Confidence 0.76 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.56 Pain Relevance 0.29
The melanocortin-4 receptor (MC4R) was cloned in 1993 by degenerate PCR; however, its function was unknown.
Gene_expression (cloned) of MC4R
8) Confidence 0.68 Published 2010 Journal Endocr. Rev. Section Abstract Doc Link 20190196 Disease Relevance 0.14 Pain Relevance 0
The melanocortin-4 receptor (MC4R) was cloned in 1993 by degenerate PCR; however, its function was unknown.
Gene_expression (cloned) of melanocortin-4 receptor
9) Confidence 0.68 Published 2010 Journal Endocr. Rev. Section Abstract Doc Link 20190196 Disease Relevance 0.14 Pain Relevance 0
2-MSH reflects autostimulation of the POMC neurones projecting to the PVN, where POMC products bind to MC4R?
Gene_expression (products) of MC4R
10) Confidence 0.66 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.68 Pain Relevance 0.37
Using techniques already described in this article, there is evidence of POMC projections from the arcuate nucleus to the DMH (Table 1; [93]) and both mc3r and mc4r mRNA are found in this nucleus (Table 3; [90,118]).
Gene_expression (projections) of mc4r in nucleus
11) Confidence 0.66 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.17 Pain Relevance 0.14
MC4R and MC3R agonists mimic the effect of ?
Gene_expression (agonists) of MC4R associated with agonist
12) Confidence 0.66 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.24 Pain Relevance 0.08
2-MSH is rather surprising, given the presence of the MC4R and the absence of the MC3R in this nucleus (Table 3; [42]).
Gene_expression (presence) of MC4R in nucleus
13) Confidence 0.66 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.05 Pain Relevance 0.11
MC4R and MC3R; feeding and obesity
Gene_expression (feeding) of MC4R associated with obesity
14) Confidence 0.66 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.53 Pain Relevance 0.42
Mice with impaired central melanocortin signaling due to targeted deletion of the MC4R (MC4RKO) are resistant to the development of cachexia in models of lipopolysaccharide (LPS) sepsis (Marks et al. 2001), cancer (Marks et al. 2001), and acute renal failure (Cheung et al. 2005).
Gene_expression (deletion) of MC4RKO associated with appetite loss, acute renal failure, cancer and sepsis
15) Confidence 0.64 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 1.17 Pain Relevance 0.19
-MSH are mediated by the melanocortin-4 receptor (MC4R), a G protein-coupled receptor expressed predominately in the brain (Cone 2005).
Gene_expression (expressed) of melanocortin-4 receptor in brain
16) Confidence 0.64 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 0.74 Pain Relevance 0.27
-MSH are mediated by the melanocortin-4 receptor (MC4R), a G protein-coupled receptor expressed predominately in the brain (Cone 2005).
Gene_expression (expressed) of MC4R in brain
17) Confidence 0.64 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 0.73 Pain Relevance 0.27
Mice with impaired central melanocortin signaling due to targeted deletion of the MC4R (MC4RKO) are resistant to the development of cachexia in models of lipopolysaccharide (LPS) sepsis (Marks et al. 2001), cancer (Marks et al. 2001), and acute renal failure (Cheung et al. 2005).
Gene_expression (deletion) of MC4R associated with appetite loss, acute renal failure, cancer and sepsis
18) Confidence 0.64 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 1.11 Pain Relevance 0.19
We next examined the kinetics of internalization of MC4R as measured by the loss of cell-surface MC4R expression.
Gene_expression (expression) of MC4R
19) Confidence 0.63 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0 Pain Relevance 0.03
MSH to the Mc4r is of particular relevance, as Mc4r is expressed in the brain and mice lacking functional Mc4r are hyperinsulinemic, hyperphagic, and obese [32].
Gene_expression (expressed) of Mc4r in brain associated with obesity
20) Confidence 0.63 Published 2004 Journal Mol Cancer Section Body Doc Link PMC443512 Disease Relevance 1.35 Pain Relevance 0.12

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