INT60957

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Context Info
Confidence 0.57
First Reported 1996
Last Reported 2009
Negated 0
Speculated 0
Reported most in Abstract
Documents 18
Total Number 18
Disease Relevance 6.00
Pain Relevance 4.73

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

transport (Abcb1b) mitochondrion (Abcb1b) ATPase activity (Abcb1b)
transmembrane transport (Abcb1b)
Anatomy Link Frequency
brain 3
testes 1
colon 1
lymphocytes 1
gut 1
Abcb1b (Mus musculus)
Pain Link Frequency Relevance Heat
fluoxetine 8 99.98 Very High Very High Very High
Pain 25 99.28 Very High Very High Very High
Analgesic 9 99.28 Very High Very High Very High
Antinociceptive 7 99.28 Very High Very High Very High
nociceptor 1 98.82 Very High Very High Very High
Opioid 15 98.20 Very High Very High Very High
agonist 22 96.64 Very High Very High Very High
Kinase C 1 96.60 Very High Very High Very High
Morphine 11 96.12 Very High Very High Very High
Serotonin 1 96.12 Very High Very High Very High
Disease Link Frequency Relevance Heat
Inflammatory Bowel Disease 64 99.84 Very High Very High Very High
Vomiting 13 98.96 Very High Very High Very High
Apoptosis 124 98.60 Very High Very High Very High
Cancer 45 97.40 Very High Very High Very High
Toxicity 13 96.52 Very High Very High Very High
Targeted Disruption 53 95.08 Very High Very High Very High
Myeloid Leukemia 39 85.44 High High
Creutzfeldt Jakob Disease 15 83.36 Quite High
Repression 7 82.36 Quite High
Breast Cancer 18 79.60 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The pronociceptive effect of ondansetron in the setting of P-glycoprotein inhibition.
Negative_regulation (inhibition) of P-glycoprotein associated with nociceptor
1) Confidence 0.57 Published 2006 Journal Anesth. Analg. Section Title Doc Link 16931690 Disease Relevance 0.40 Pain Relevance 0.62
Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier.
Negative_regulation (inhibition) of P-glycoprotein in lymphocytes associated with analgesic
2) Confidence 0.57 Published 2006 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 16537797 Disease Relevance 0 Pain Relevance 0.46
Although the phenomenon would certainly be rare [56], one may imagine that some individuals present a genetic deficiency in BBB P-glycoproteins.
Negative_regulation (deficiency) of P-glycoprotein
3) Confidence 0.57 Published 2003 Journal Filaria J Section Body Doc Link PMC2147657 Disease Relevance 0.06 Pain Relevance 0.04
Some compounds increased the Cl(up) of verapamil in P-gp-competent mice, consistent with P-gp inhibition.
Negative_regulation (inhibition) of P-gp
4) Confidence 0.57 Published 2002 Journal J Pharm Sci Section Abstract Doc Link 11782913 Disease Relevance 0 Pain Relevance 0.13
Inhibition of P-gp may thus result in higher brain uptake of M6G.
Negative_regulation (Inhibition) of P-gp in brain
5) Confidence 0.57 Published 2000 Journal Life Sci. Section Abstract Doc Link 10864101 Disease Relevance 0.23 Pain Relevance 0.61
Genetic or chemical disruption of P-gp has been shown to enhance the antinociceptive and/or toxic effects of some opioids, although the extent of this phenomenon has yet to be understood.
Negative_regulation (disruption) of P-gp associated with opioid and antinociceptive
6) Confidence 0.42 Published 2004 Journal Biochem. Pharmacol. Section Abstract Doc Link 14698039 Disease Relevance 0 Pain Relevance 0.61
We conclude that despite reported doubling of M6G brain uptake, absence of mdr1a coded P-gp does not enhance antinociceptive effects of M6G in the hotplate test after acute single-dose administration in mdr1a(-/-) knockout mice.
Negative_regulation (absence) of P-gp in brain associated with targeted disruption and antinociceptive
7) Confidence 0.42 Published 2000 Journal Life Sci. Section Abstract Doc Link 10864101 Disease Relevance 0.54 Pain Relevance 0.42
Vanadate also inhibits the multi-drug transporter protein, P-glycoprotein (Urbatsch et al. 1995, Taguchi et al. 1997), responsible for exporting toxic chemicals from cells and is known to disrupt the transport functions of most ATP-binding casette proteins (Terasaka et al. 2003).
Negative_regulation (inhibits) of P-glycoprotein
8) Confidence 0.42 Published 2007 Journal The Journal of Endocrinology Section Body Doc Link PMC2173947 Disease Relevance 0.65 Pain Relevance 0
Cyclosporine's central actions can be better evaluated in mdr1a knockout mice that lack P-glycoprotein.
Negative_regulation (lack) of P-glycoprotein
9) Confidence 0.42 Published 2007 Journal Anesth. Analg. Section Body Doc Link 17959987 Disease Relevance 0 Pain Relevance 0
Tariquidar and elacridar, potent and selective P-glycoprotein inhibitors, were investigated in this regard using the opioid loperamide as an in vivo probe in mice.
Negative_regulation (inhibitors) of P-glycoprotein associated with opioid
10) Confidence 0.42 Published 2006 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 16537797 Disease Relevance 0 Pain Relevance 0.18
As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR0/0 mice that are deficient in mdr1a and mdr1b genes.
Negative_regulation (deficient) of mdr1b
11) Confidence 0.41 Published 2009 Journal PLoS Pathogens Section Abstract Doc Link PMC2777304 Disease Relevance 0.23 Pain Relevance 0
When treated with ivermectin, animals presenting a deficiency in P-glycoproteins develop a toxicosis related to high concentrations of the drug in the brain [54,55].
Negative_regulation (deficiency) of P-glycoprotein in brain
12) Confidence 0.41 Published 2003 Journal Filaria J Section Body Doc Link PMC2147657 Disease Relevance 0.06 Pain Relevance 0.04
Moreover, fluoxetine reversed MDR at doses that are well below its human safety limits, free of the severe dose-related toxicity, adverse effects, and poor solubility that are obstacles to other chemosensitizers.
Negative_regulation (reversed) of MDR associated with toxicity and fluoxetine
13) Confidence 0.36 Published 2004 Journal Cancer Res. Section Abstract Doc Link 15492283 Disease Relevance 0.63 Pain Relevance 0.70
This could lead directly (through changes in membrane permeability and fluidity) and/or indirectly (through inhibition of P-glycoprotein phosphorylation via inhibition of the phosphatidylserine-dependent protein kinase C or changes in the conformation and functioning of the membrane-integrated proteins via changes in the structure organization of the surrounding membrane bilayer) to the reversal of MDR.
Negative_regulation (reversal) of MDR associated with kinase c
14) Confidence 0.26 Published 1996 Journal J. Cancer Res. Clin. Oncol. Section Abstract Doc Link 8543589 Disease Relevance 0.23 Pain Relevance 0.10
There-fore, imatinib inhibition of ABCB1-mediated efflux may be the cause for the increased IUR for nilotinib that is observed when both drugs are combined (White et al 2007).


Negative_regulation (inhibition) of ABCB1
15) Confidence 0.23 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 0.38 Pain Relevance 0
Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier.
Negative_regulation (inhibition) of P-glycoprotein in testes associated with analgesic
16) Confidence 0.19 Published 2006 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 16537797 Disease Relevance 0 Pain Relevance 0.46
Although the downregulation of MDR1 in IBD patients may be independent of the decreased expression of SXR, these data are consistent with the possibility that dysregulation of SXR in the gut is likely to contribute to the pathophysiology of ulcerative colitis.
Negative_regulation (downregulation) of MDR1 in gut associated with inflammatory bowel disease
17) Confidence 0.10 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 1.36 Pain Relevance 0.19
They further showed, using DNA microarray analyses of nonaffected tissue from IBD patients, that expression of SXR and a known target gene, MDR1, were downregulated in the colon of ulcerative colitis patients.
Negative_regulation (downregulated) of MDR1 in colon associated with inflammatory bowel disease
18) Confidence 0.08 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 1.23 Pain Relevance 0.18

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