INT210838

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Context Info
Confidence 0.53
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 17
Total Number 18
Disease Relevance 6.79
Pain Relevance 3.06

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
hypothalamus 4
arcuate nucleus 1
nerve 1
Mc4r (Mus musculus)
Pain Link Frequency Relevance Heat
agonist 198 99.96 Very High Very High Very High
5HT 18 99.60 Very High Very High Very High
bDMF 12 99.18 Very High Very High Very High
Central nervous system 83 99.08 Very High Very High Very High
melanocortin 1 receptor 70 98.22 Very High Very High Very High
Spinal cord 4 93.36 High High
Inflammation 33 91.00 High High
antagonist 78 89.60 High High
Potency 45 88.24 High High
medulla 136 87.00 High High
Disease Link Frequency Relevance Heat
Obesity 419 99.72 Very High Very High Very High
Appetite Loss 95 99.16 Very High Very High Very High
Body Weight 85 97.04 Very High Very High Very High
Nervous System Injury 2 96.76 Very High Very High Very High
Anorexia 70 94.72 High High
Injury 18 94.56 High High
Sprains And Strains 35 93.04 High High
INFLAMMATION 34 91.00 High High
Myocardial Infarction 104 90.28 High High
Leukemia 1 87.20 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Following axotomy, no alteration in MC1R mRNA expression is seen in dorsal root ganglia and decreases in both MC2R and MC3R, but MC4R mRNA increases following axotomy [48], perhaps suggesting a greater role for MC4R than MC1R in nerve injury.
Positive_regulation (increases) of MC4R in nerve associated with nervous system injury and melanocortin 1 receptor
1) Confidence 0.53 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 1.06 Pain Relevance 1.06
Wild-type MC4R was activated by ?
Positive_regulation (activated) of MC4R
2) Confidence 0.49 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.09 Pain Relevance 0.04
mc4r mRNA and MC4R protein is concentrated in the feeding areas of the PVN, DMH and lateral hypothalamus [90,105].
Positive_regulation (concentrated) of MC4R in hypothalamus
3) Confidence 0.49 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.75 Pain Relevance 0.19
mc4r mRNA and MC4R protein is concentrated in the feeding areas of the PVN, DMH and lateral hypothalamus [90,105].
Positive_regulation (concentrated) of mc4r in hypothalamus
4) Confidence 0.49 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.76 Pain Relevance 0.19
Whilst not being shown to activate hypothalamic neurones in vivo [42], it binds to and activates both MC3R and MC4R in vitro and has an anorectic effect at high doses in vivo [123].
Positive_regulation (activates) of MC4R associated with appetite loss
5) Confidence 0.46 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.30 Pain Relevance 0
All the experiments performed in this hypothalamic cell line showed that COUP-TFII gene expression was increased by an activation of the MC4-R signaling pathway.
Positive_regulation (activation) of MC4-R
6) Confidence 0.45 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956692 Disease Relevance 0 Pain Relevance 0.23
This observation raises the possibility that increased peripheral MC4R signaling may be contributing to the pathogenesis of cardiac cachexia, and that blockade of this signaling as would occur with MC4RKO mice might contribute to the prevention of cardiac cachexia.
Positive_regulation (increased) of MC4R associated with appetite loss
7) Confidence 0.42 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 0.72 Pain Relevance 0.17
However, a detailed, mechanistic understanding of the cellular and biochemical changes in the hypothalamus in response to MC4R signaling has been difficult to elucidate because of the presence of the endogenous hormone, ?
Positive_regulation (response) of MC4R in hypothalamus
8) Confidence 0.41 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.20 Pain Relevance 0.11
We next determined the ability of these mutated receptors to respond to the synthetic ligand THIQ, a selective MC4R agonist that potently stimulates cAMP production in the wild-type receptor in vitro [21] (EC50?
Positive_regulation (selective) of MC4R associated with agonist
9) Confidence 0.41 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.25 Pain Relevance 0.05
Having two RASSLs with different basal activities would be especially useful because in vitro and indirect in vivo [52] evidence suggest that the basal activity of MC4R may also be important these processes.
Positive_regulation (important) of MC4R
10) Confidence 0.41 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.20 Pain Relevance 0
Engineering the Melanocortin-4 Receptor to Control Constitutive and Ligand-Mediated Gs Signaling In Vivo

The molecular and functional diversity of G protein–coupled receptors is essential to many physiological processes.

Positive_regulation (Engineering) of Melanocortin-4 Receptor
11) Confidence 0.41 Published 2007 Journal PLoS ONE Section Title Doc Link PMC1930153 Disease Relevance 0.07 Pain Relevance 0
-MSH is not produced physiologically in rodents [7,120] and so any observed effects could be through pharmacological activation of the MC4R?
Positive_regulation (activation) of MC4R
12) Confidence 0.40 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.51 Pain Relevance 0.07
POMC neurones in the arcuate nucleus, acting on other feeding areas such as the PVN via MC4R activation, may be the principal CNS conduit for leptin's peripheral satiety signal.


Positive_regulation (activation) of MC4R in arcuate nucleus associated with central nervous system
13) Confidence 0.40 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.99 Pain Relevance 0.24
MC4R is stimulated by the endogenous ligand ?
Positive_regulation (stimulated) of MC4R
14) Confidence 0.38 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.29 Pain Relevance 0.27
-MSH-mediated activation in the human MC4R mutations is thought to be the basis of the obesity in patients carrying these mutations.
Positive_regulation (activation) of MC4R associated with obesity
15) Confidence 0.36 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.24 Pain Relevance 0.04
It will be interesting to compare Gs-mediated signaling from the RASSLs based on the 5HT-4 receptor and the MC4R for receptor-specific differences in Gs protein activation in the same cell types in vivo.
Positive_regulation (activation) of MC4R associated with 5ht
16) Confidence 0.33 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0 Pain Relevance 0.14
-MSH elicited full activation of wild-type MC4R (EC50?
Positive_regulation (activation) of MC4R
17) Confidence 0.33 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1930153 Disease Relevance 0.06 Pain Relevance 0.08
In the VMH and the dorsomedial hypothalamus, the BDNF gene expression is clearly modulated by MC4-R activation and several lines of evidence have also identified the Single Minded 1 as a downstream target of MC4-R in the paraventricullar hypothalamus [50], [51].
Positive_regulation (activation) of MC4-R in hypothalamus associated with bdmf
18) Confidence 0.26 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956692 Disease Relevance 0.29 Pain Relevance 0.18

General Comments

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