INT97448

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Context Info
Confidence 0.58
First Reported 2001
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 20
Total Number 23
Disease Relevance 7.37
Pain Relevance 12.91

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

pigmentation (Mc1r) signal transduction (Mc1r) plasma membrane (Mc1r)
signal transducer activity (Mc1r)
Anatomy Link Frequency
melanocytes 3
pigmentation 2
DMNV 1
skin 1
Mc1r (Mus musculus)
Pain Link Frequency Relevance Heat
melanocortin 1 receptor 752 100.00 Very High Very High Very High
GABAergic 3 100.00 Very High Very High Very High
agonist 55 99.62 Very High Very High Very High
vagus nerve 6 98.70 Very High Very High Very High
antagonist 34 98.52 Very High Very High Very High
qutenza 98 97.36 Very High Very High Very High
analgesia 36 93.08 High High
Acute pain 8 91.56 High High
medulla 1 91.44 High High
Eae 64 88.96 High High
Disease Link Frequency Relevance Heat
Targeted Disruption 30 100.00 Very High Very High Very High
Apoptosis 30 98.84 Very High Very High Very High
Burns 25 98.76 Very High Very High Very High
Skin Cancer 257 97.68 Very High Very High Very High
Cancer 51 94.64 High High
Obesity 16 94.24 High High
Pain 96 91.56 High High
Inflammatory Pain 36 88.96 High High
Microphthalmia 8 88.00 High High
Hyperalgesia 52 86.32 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Furthermore, the possibility that other melanocortin receptors might compensate when both MC1R and MC4R are blocked cannot be ruled out.
Negative_regulation (blocked) of MC1R associated with melanocortin 1 receptor
1) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.70 Pain Relevance 1.07
Agouti, the ligand of Mc1r, is an inverse agonist that, when bound, reduces Mc1r activity (via lowered cAMP signaling) resulting in lighter pigmentation.
Negative_regulation (reduces) of Mc1r in pigmentation associated with melanocortin 1 receptor and agonist
2) Confidence 0.58 Published 2007 Journal PLoS Biol Section Body Doc Link PMC1945039 Disease Relevance 0 Pain Relevance 0.84
Here, we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci.
Negative_regulation (defective) of melanocortin 1 receptor associated with targeted disruption and melanocortin 1 receptor
3) Confidence 0.53 Published 2009 Journal Pigment Cell Melanoma Res Section Abstract Doc Link 19682281 Disease Relevance 0.18 Pain Relevance 0.10
Here, we extend this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci.
Negative_regulation (defective) of Mc1r associated with targeted disruption and melanocortin 1 receptor
4) Confidence 0.53 Published 2009 Journal Pigment Cell Melanoma Res Section Abstract Doc Link 19682281 Disease Relevance 0.18 Pain Relevance 0.10
In B 16F1 cells, a single injection of 50 to 500 microg alpha-MSH induced a rapid but moderate dose-dependent MC1R down-regulation which could be totally reverted within 16-24 h.
Negative_regulation (down-regulation) of MC1R associated with melanocortin 1 receptor
5) Confidence 0.51 Published 2002 Journal J. Recept. Signal Transduct. Res. Section Abstract Doc Link 12503610 Disease Relevance 0.40 Pain Relevance 0.88
By continuous administration of alpha-MSH via osmotic minipumps, MC1R down-regulation was considerably amplified and reached the level observed in vitro, demonstrating that prolonged receptor interaction was necessary to induce a maximal effect in vivo.
Negative_regulation (down-regulation) of MC1R associated with melanocortin 1 receptor
6) Confidence 0.51 Published 2002 Journal J. Recept. Signal Transduct. Res. Section Abstract Doc Link 12503610 Disease Relevance 0.39 Pain Relevance 0.93
Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned' individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R).
Negative_regulation (disruption) of melanocortin 1 receptor associated with melanocortin 1 receptor
7) Confidence 0.43 Published 2006 Journal Nature Section Abstract Doc Link 16988713 Disease Relevance 0 Pain Relevance 0.48
Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned' individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R).
Negative_regulation (disruption) of MC1R associated with melanocortin 1 receptor
8) Confidence 0.43 Published 2006 Journal Nature Section Abstract Doc Link 16988713 Disease Relevance 0 Pain Relevance 0.48
However, recent studies by Abdel-Malek and colleagues [67] indicate that MC1R deficiency causes increased UV-induced apoptosis in cultured melanocytes.
Negative_regulation (deficiency) of MC1R in melanocytes associated with melanocortin 1 receptor and apoptosis
9) Confidence 0.43 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1774588 Disease Relevance 0.55 Pain Relevance 0.53
Indeed, previous work from our group and others indicates that while Mc1r expression is confined mainly to melanocytes, Mc1r deficiency leads to substantial changes in gene expression throughout the skin and suggests that melanocytes influence the behavior of surrounding cells via paracrine mechanisms.
Negative_regulation (deficiency) of Mc1r in skin
10) Confidence 0.43 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1774588 Disease Relevance 0.43 Pain Relevance 0.44
Animals without viable melanocytes (KitW-v/KitW-v) or animals lacking a functional Mc1r (Mc1re/Mc1re) were exposed to sunburn-level doses of UVB radiation, and the patterns of large-scale gene expression in the basal epidermis were compared to each other and to nonmutant animals.
Negative_regulation (lacking) of Mc1r in melanocytes associated with burns
11) Confidence 0.43 Published 2007 Journal PLoS Genetics Section Abstract Doc Link PMC1774588 Disease Relevance 0.48 Pain Relevance 0.25
Thus, the light color pattern of beach mice largely results from the physical interaction between a structural change in a receptor (reducing Mc1r activity) and a regulatory change in the receptor's antagonist (increasing Agouti expression).



Negative_regulation (reducing) of Mc1r associated with melanocortin 1 receptor and antagonist
12) Confidence 0.43 Published 2007 Journal PLoS Biol Section Abstract Doc Link PMC1945039 Disease Relevance 0 Pain Relevance 0.46
Thus, a more likely scenario is that decreased MC1R signaling in melanocytes exposed to UV radiation in vivo impairs the ability of surrounding cells to undergo p53-mediated cell cycle arrest and apoptosis.
Negative_regulation (decreased) of MC1R in melanocytes associated with melanocortin 1 receptor and apoptosis
13) Confidence 0.42 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1774588 Disease Relevance 0.49 Pain Relevance 0.51
We offered mice lacking Mc1r and transgenic, human MC1R-positive littermate controls, a choice of water or highly dilute capsaicin, and assessed their consumption over a period of 10 days.
Negative_regulation (lacking) of Mc1r associated with targeted disruption, qutenza and melanocortin 1 receptor
14) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.63 Pain Relevance 1.20
Second, both structural mutations (a single amino acid change reducing Mc1r signaling potential) and regulatory mutations (a derived increase in Agouti expression) contribute to adaptive change, and this change involves both recessive (Mc1r L) and dominant (Agouti L) alleles.
Negative_regulation (reducing) of Mc1r associated with melanocortin 1 receptor
15) Confidence 0.42 Published 2007 Journal PLoS Biol Section Body Doc Link PMC1945039 Disease Relevance 0.05 Pain Relevance 0.37
l 20× TaqMan gene expression assay of Agouti, Mc1r, and beta-Actin.
Negative_regulation (assay) of Mc1r associated with melanocortin 1 receptor
16) Confidence 0.42 Published 2007 Journal PLoS Biol Section Body Doc Link PMC1945039 Disease Relevance 0 Pain Relevance 0.23
Coupling to inositol triphosphate (IP3) and Ca2+signaling (which Gq and phospholipase C could mediate) has been reported for a number of human and mouse melanocortin receptors, including MC1R (Eves et al., 2003; García-Borrón et al., 2005; Mountjoy et al., 2001).
Negative_regulation (number) of MC1R associated with melanocortin 1 receptor
17) Confidence 0.41 Published 2009 Journal Pigment Cell & Melanoma Research Section Body Doc Link PMC2784899 Disease Relevance 0.16 Pain Relevance 0.38
In addition to effects on pigmentation, MC1R loss of function is associated with an increased incidence of melanoma and nonmelanoma skin cancer in Australian [22,23], Mediterranean [24–26], and northern European [27,28] populations.
Negative_regulation (loss) of MC1R in pigmentation associated with melanocortin 1 receptor and skin cancer
18) Confidence 0.37 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC1774588 Disease Relevance 0.49 Pain Relevance 0.55
We have tested responses to noxious and non-noxious stimuli in mutant mice which lack MC1R, or which overexpress an endogenous antagonist of the receptor, as well as controls.
Negative_regulation (lack) of MC1R associated with antagonist
19) Confidence 0.37 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2938350 Disease Relevance 0.81 Pain Relevance 0.93
We offered mice lacking Mc1r and transgenic, human MC1R-positive littermate controls, a choice of water or highly dilute capsaicin, and assessed their consumption over a period of 10 days.
Negative_regulation (lacking) of MC1R associated with targeted disruption, qutenza and melanocortin 1 receptor
20) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2938350 Disease Relevance 0.63 Pain Relevance 1.21

General Comments

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