INT105609

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Context Info
Confidence 0.58
First Reported 2002
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 10
Total Number 13
Disease Relevance 10.40
Pain Relevance 5.04

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
nerve 1
brain 1
hindlimb 1
hearts 1
Mc4r (Mus musculus)
Pain Link Frequency Relevance Heat
antagonist 52 100.00 Very High Very High Very High
melanocortin 1 receptor 292 99.90 Very High Very High Very High
agonist 66 99.36 Very High Very High Very High
Glutamate 2 94.44 High High
Inflammation 91 89.92 High High
Central nervous system 40 87.52 High High
nociceptor 12 84.88 Quite High
Spinal cord 16 83.56 Quite High
Quantitative sensory testing 4 83.36 Quite High
TRP channel 16 80.12 Quite High
Disease Link Frequency Relevance Heat
Obesity 168 99.68 Very High Very High Very High
Appetite Loss 155 99.54 Very High Very High Very High
Targeted Disruption 103 99.28 Very High Very High Very High
Injury 72 98.84 Very High Very High Very High
Hyperphagia 12 98.20 Very High Very High Very High
Myocardial Infarction 312 97.92 Very High Very High Very High
Chronic Disease 12 95.24 Very High Very High Very High
Pulmonary Edema 18 94.76 High High
Nervous System Injury 8 94.68 High High
INFLAMMATION 95 89.92 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In addition, the effects of morphine were evaluated in A(y) mice, a genetic model for MC4 receptor blockade.
Negative_regulation (blockade) of MC4
1) Confidence 0.58 Published 2005 Journal Psychopharmacology (Berl.) Section Body Doc Link 15719225 Disease Relevance 0 Pain Relevance 0
It is also worth noting that the Ay-Jkn1 mice are obese as a result of inhibiting the MC4R, and the role that this has to play in terms of behavioural reflex assessment of the hindlimb needs further clarification.
Negative_regulation (inhibiting) of MC4R in hindlimb associated with obesity
2) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.63 Pain Relevance 0.98
Furthermore, the possibility that other melanocortin receptors might compensate when both MC1R and MC4R are blocked cannot be ruled out.
Negative_regulation (blocked) of MC4R associated with melanocortin 1 receptor
3) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.70 Pain Relevance 1.07
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.
Negative_regulation (loss) of MC4R associated with targeted disruption, melanocortin 1 receptor and antagonist
4) Confidence 0.43 Published 2002 Journal Neuropeptides Section Abstract Doc Link 12359499 Disease Relevance 0.53 Pain Relevance 0.14
OBJECTIVES: The goal of this study was to test the hypothesis that blockade of MC4 receptors increases the behavioral effects of morphine.
Negative_regulation (blockade) of MC4
5) Confidence 0.42 Published 2005 Journal Psychopharmacology (Berl.) Section Body Doc Link 15719225 Disease Relevance 0 Pain Relevance 0
However, mice lacking both mc3r and mc4r are more obese than mc4r ko mice alone [112,113].
Negative_regulation (lacking) of mc4r associated with obesity
6) Confidence 0.42 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 1.16 Pain Relevance 0.19
These results argue that in addition to attenuating cachexia in the acute illness, loss of MC4R signaling is also effective in providing prolonged protection against the development of cachexia in the setting of a chronic illness.
Negative_regulation (loss) of MC4R associated with appetite loss and chronic disease
7) Confidence 0.41 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 1.03 Pain Relevance 0.03
One concern at the beginning of the study is that loss of MC4R signaling could potentially alter the sensitivity of the hearts to the effects of the MI procedure.
Negative_regulation (loss) of MC4R in hearts associated with myocardial infarction
8) Confidence 0.41 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 1.74 Pain Relevance 0
These results argue against the loss of MC4R signaling providing a protective effect against ischemic damage as a result of the MI procedure, or altering the subsequent development of cardiohypertrophy.
Negative_regulation (loss) of MC4R associated with myocardial infarction
9) Confidence 0.41 Published 2010 Journal The Journal of Endocrinology Section Body Doc Link PMC2887273 Disease Relevance 1.56 Pain Relevance 0
Gain of function mutations of the gene encoding ASP in the mouse can result in increased and widespread expression of the protein, leading to a yellow coat through action on MC1R, but also to obesity through ectopic inactivation of MC4R [23].
Negative_regulation (inactivation) of MC4R associated with melanocortin 1 receptor and obesity
10) Confidence 0.39 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.44 Pain Relevance 1.02
AgRP – more than an antagonist of MC4R and MC3R?
Negative_regulation (antagonist) of MC4R associated with antagonist
11) Confidence 0.37 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.30 Pain Relevance 0.40
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].
Negative_regulation (lacking) of Mc4r in brain associated with obesity
12) Confidence 0.34 Published 2004 Journal Mol Cancer Section Body Doc Link PMC443512 Disease Relevance 1.37 Pain Relevance 0.12
However, we observed no alteration or reduced development of nerve-injury induced behavioural sensitisation in Ay-Jkn1 mice, where MC4R function is also blocked by the inverse agonist ASP.
Negative_regulation (blocked) of MC4R in nerve associated with injury and agonist
13) Confidence 0.32 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.94 Pain Relevance 1.08

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