INT25271

Context Info Confidence 0.67 First Reported 1983 Last Reported 2010 Negated 0 Speculated 2 Reported most in Abstract Documents 21 Total Number 24 Disease Relevance 13.59 Pain Relevance 5.96

mitochondrion (MTG1) nucleolus (MTG1) nucleus (MTG1)

Anatomy Link Frequency brain structures 2 poly 1 glial cell 1 MTG1 (Homo sapiens)

Pain Link Frequency Relevance Heat opioid receptor 5 100.00 Opioid 8 99.68 Cannabinoid 4 98.96 agonist 24 98.52 opiate 2 98.52 Morphine 10 97.16 Sumatriptan 4 96.78 tolerance 18 95.28 Pain 21 94.48 Potency 2 94.12

Disease Link Frequency Relevance Heat Leukocytosis 2 99.90 Syndrome 21 99.88 Toxicity 42 99.80 Disease 397 99.62 Metastasis 6 99.44 Pressure And Volume Under Development 4 98.40 Stomach Cancer 3 98.20 Adenocarcinoma 5 97.76 Ocular Toxicity (including Many Sub-types) 1 96.88 Congenital Anomalies 9 96.84

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In the present study, we have further explored this issue by examining density, mRNA expression and activation of GTP-binding proteins for the cannabinoid CB1 receptor subtype in several brain structures of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), a chronic model of MS that reproduces many of the pathological hallmarks of the human disease.

Spec (examining) Positive_regulation (activation) of GTP in brain structures associated with multiple sclerosis, cannabinoid, disease and experimental autoimmune encephalomyelitis

1) Confidence 0.67 Published 2006 Journal Brain Res. Section Abstract Doc Link 16822488 Disease Relevance 1.16 Pain Relevance 0.37

High activities of serum AIP, LAP and gamma-GTP were observed.

Positive_regulation (activities) of GTP

2) Confidence 0.67 Published 1988 Journal Hokkaido Igaku Zasshi Section Abstract Doc Link 3283015 Disease Relevance 1.00 Pain Relevance 0.13

Frequency of the arterial hypertension was the same in both groups, whereas acroparesthesias, Raynaud's syndrome, and increased gamma GTP serum activity were significantly more frequent in workers with neurological disturbances.

Positive_regulation (increased) of GTP associated with pressure and volume under development and syndrome

3) Confidence 0.67 Published 1983 Journal Int Arch Occup Environ Health Section Abstract Doc Link 6629505 Disease Relevance 0.88 Pain Relevance 0.08

Aluminum fluoride, known to activate GTP binding proteins, also reduced potentials and this was antagonized by morphine.

Positive_regulation (activate) of GTP associated with morphine

4) Confidence 0.67 Published 1995 Journal Pharmacol. Res. Section Abstract Doc Link 7596956 Disease Relevance 0 Pain Relevance 0.80

Furthermore, expression of epidermal growth factor receptor (EGFR) and its ligands; serine protease inhibitor Kazal type 3 (Spink3) and transforming growth factor alpha (TGF alpha) and activation of K-Ras (GTP-Ras formation), which are frequently observed in human PDA, were indeed observed in parallel with TCs formation.

Positive_regulation (activation) of GTP associated with adenocarcinoma

5) Confidence 0.49 Published 2010 Journal Exp. Anim. Section Abstract Doc Link 20660988 Disease Relevance 0.88 Pain Relevance 0.43

The inward current induced by VIP became irreversible after the intracellular administration of GTP gamma S, a hydrolysis-resistant analog of GTP which can cause a prolonged activation of G-proteins.

Positive_regulation (activation) of GTP

6) Confidence 0.49 Published 1989 Journal Brain Res. Section Abstract Doc Link 2514005 Disease Relevance 0.09 Pain Relevance 0.24

Further, (+)-5a potently stimulated GTP gamma S binding to NOP membranes (EC50 = 65 nM) and inhibited forskolin-mediated cAMP accumulation in NOP-expressing cells (EC50 = 9.1 nM) with a potency comparable to that of the natural peptide agonist N/OFQ.

Positive_regulation (stimulated) of GTP associated with agonist and potency

7) Confidence 0.49 Published 2003 Journal J. Med. Chem. Section Abstract Doc Link 12519064 Disease Relevance 0 Pain Relevance 0.48

It further appeared that 6-times more h5-HT1D than h5-HT1B binding sites were required to attain a similar, maximal (73%), 5-HT-stimulated [35S]GTP gamma S binding response: Hence, the h5-HT1B receptor in C6-glial cell membranes could be more efficiently coupled, even though some compounds more readily displayed intrinsic activity at h5-HT1D receptor sites [e.g. dihydroergotamine and (2'-methyl-4'-(5-methyl[1,2,4]oxadiazol-3-yl)biphenyl-4-carboxylic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide (GR127935)].

Positive_regulation (5-HT-stimulated) of GTP in glial cell

8) Confidence 0.49 Published 1997 Journal Neuropharmacology Section Abstract Doc Link 9225275 Disease Relevance 0 Pain Relevance 0.13

Efficacy differences were apparent for most of the compounds (sumatriptan, zolmitriptan, rizatriptan, N-methyl-3-[pyrrolidin-2(R)-ylmethyl]-1H-indol-5-ylmethyl sulfonamide (CP122638), dihydroergotamine, naratriptan and GR127935) that stimulated [35S]GTP gamma S binding compared to the native agonist 5-HT.

Positive_regulation (stimulated) of GTP associated with sumatriptan and agonist

9) Confidence 0.49 Published 1997 Journal Neuropharmacology Section Abstract Doc Link 9225275 Disease Relevance 0 Pain Relevance 0.33

N/OFQ stimulation increased [35S]GTP gamma S binding to cell membranes and attenuated forskolin-induced cAMP accumulation in a concentration-dependent manner.

Positive_regulation (increased) of GTP

10) Confidence 0.49 Published 1997 Journal Neuroreport Section Abstract Doc Link 9223076 Disease Relevance 0.25 Pain Relevance 0.30

Biochemical, pharmacological and molecular biology studies suggest several molecular mechanisms of the bimodal activity of opioids, including the coupling of opioid receptors to various GTP-binding proteins, the involvement of different subunits of these proteins, and the activation of several intracellular signal transduction pathways.

Positive_regulation (coupling) of GTP associated with opioid receptor and opioid

11) Confidence 0.49 Published 1996 Journal Neurochem. Res. Section Abstract Doc Link 8947925 Disease Relevance 0.08 Pain Relevance 0.85

Under the conditions of the [35S]GTP gamma S assay, binding of agonists was to a high affinity site, indicating that a high agonist affinity state of the mu-opioid receptor is responsible for the observed stimulation of [35S]GTP gamma S binding.

Spec (observed) Positive_regulation (stimulation) of GTP associated with agonist and opioid receptor

12) Confidence 0.49 Published 1995 Journal Mol. Pharmacol. Section Abstract Doc Link 7723747 Disease Relevance 0.13 Pain Relevance 1.52

The serum LDH, GOT, GPT, ALP and gamma-GTP levels were elevated, and antibodies to Epstein-Barr viral capsid, early, and nuclear antigens were diagnostic of a primary Epstein-Barr virus infection.

Positive_regulation (elevated) of gamma-GTP associated with infection

13) Confidence 0.08 Published 1996 Journal Rinsho Ketsueki Section Abstract Doc Link 8827884 Disease Relevance 0.52 Pain Relevance 0.09

Laboratory data other than leukocytosis and elevated level of gamma-GTP were normal and the results of brain CT scan were within normal limits.

Positive_regulation (elevated) of gamma-GTP in brain associated with leukocytosis

14) Confidence 0.07 Published 1989 Journal Rinsho Shinkeigaku Section Abstract Doc Link 2612105 Disease Relevance 1.35 Pain Relevance 0.09

The net effect of unregulated activation and inactivation is a subtle increase in the duration of association of active Rab7 with target membranes and an increase in the GTP-bound, active fraction (Figs. 3, 4, and 5).

Positive_regulation (increase) of GTP

15) Confidence 0.02 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.40 Pain Relevance 0

This finding indicates that accelerated GTP exchange in disease mutants leads to an increase in the active, GTP-bound fraction of Rab7.

Positive_regulation (increase) of GTP associated with disease

16) Confidence 0.02 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.44 Pain Relevance 0

Although a previous report concluded that disease mutants have a GTPase defect (21), we demonstrate that this apparent defect is largely a reflection of increased GTP dissociation.

Positive_regulation (increased) of GTP associated with disease

17) Confidence 0.02 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.38 Pain Relevance 0

We found that the Rab7 compound mutants largely rescued the FRAP defect seen in the Q67L mutant alone, suggesting that the Rab7 disease-causing mutations increase GTP dissociation and lead to GTPase-independent membrane cycling of Rab7 in vivo (Fig. 6C).

Positive_regulation (increase) of GTP associated with disease

18) Confidence 0.02 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.41 Pain Relevance 0

Surprisingly, the cellular phenotype of mutant Rab7 is milder than expected given the prominent, unregulated GTP exchange and marked increase in the active fraction.

Positive_regulation (increase) of GTP

19) Confidence 0.02 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.42 Pain Relevance 0

Up to the 25 mg/kg dose level, one DLT (Grade 3 gamma-GTP increase at a dose of 25 mg/kg) was observed.

Positive_regulation (increase) of gamma-GTP associated with toxicity

20) Confidence 0.01 Published 2009 Journal Japanese Journal of Clinical Oncology Section Body Doc Link PMC2661001 Disease Relevance 1.78 Pain Relevance 0

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