INT34829

Context Info Confidence 0.46 First Reported 1986 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 27 Total Number 28 Disease Relevance 5.24 Pain Relevance 4.14

signal transduction (Gnat3) GTPase activity (Gnat3) cytoplasm (Gnat3) signal transducer activity (Gnat3)

Anatomy Link Frequency aorta 1 brachial artery 1 Gnat3 (Mus musculus)

Pain Link Frequency Relevance Heat tolerance 217 100.00 headache 46 99.52 Potency 33 99.20 Angina 23 98.52 transdermal 11 96.64 Migraine 11 92.48 Pain 3 90.56 Cluster headache 2 87.40 anesthesia 4 76.76 addiction 20 74.96

Disease Link Frequency Relevance Heat Headache 45 99.52 Pancreatitis 70 98.98 Coronary Artery Disease 20 98.60 Cv General 3 Under Development 17 98.52 Cv Unclassified Under Development 2 95.88 Reprotox - General 2 3 94.52 Dizziness 1 94.28 Increased Venous Pressure Under Development 74 91.84 Pain 3 90.56 Stress 75 87.92

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Whereas the increase in transdermally absorbed GTN may be beneficial to the exercising angina patient, increased effects of GTN may be undesirable in hot surroundings.

Positive_regulation (increase) of GTN associated with angina

1) Confidence 0.46 Published 1986 Journal Am. Heart J. Section Abstract Doc Link 3092610 Disease Relevance 0.28 Pain Relevance 0.40

Ethanol in turn could interfere with GTN bioactivation by the formation of the natural substrate and competitive inhibitor of bioactivation acetaldehyde.

Positive_regulation (bioactivation) of GTN

2) Confidence 0.34 Published 2006 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1654181 Disease Relevance 0.12 Pain Relevance 0.12

This was an important finding with respect to our recent observation that mitochondrial ROS levels were significantly increased upon GTN in vivo treatment of Mn-SOD+/- mice [23] which was reproduced with the present findings (Figure 2A).

Positive_regulation (increased) of GTN

3) Confidence 0.34 Published 2006 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1654181 Disease Relevance 0.15 Pain Relevance 0.23

M) induced in vitro tolerance (tachyphylaxis) to the finally applied nitrate GTN.

Positive_regulation (induced) of GTN associated with tolerance

4) Confidence 0.34 Published 2006 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1654181 Disease Relevance 0.17 Pain Relevance 0.43

At sufficiently high concentrations, ascorbate can substitute for Cys in the activation of GTN (8).

Positive_regulation (activation) of GTN

5) Confidence 0.30 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0.16 Pain Relevance 0.14

The residual activity and the extent of restoration in the presence of DTT diminished when the concentration of GTN was increased (Fig. 1B).

Positive_regulation (increased) of GTN

6) Confidence 0.30 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0

So widespread prophylactic administration of GTN may significantly reduce the incidence of PEP, resulting in major clinical and economic benefit especially for those centers with a high incidence of PEP, because compared with other prophylactic agents, GTN not only is effective and can be expediently or easily administrated, but is cheap.

Positive_regulation (effective) of GTN associated with pancreatitis

7) Confidence 0.29 Published 2010 Journal BMC Gastroenterol Section Body Doc Link PMC2921391 Disease Relevance 0.58 Pain Relevance 0.03

Rats that received more than 8 IS infusions showed a marked increase in their neurochemical and behavioral responses to GTN.

Positive_regulation (increase) of GTN

8) Confidence 0.26 Published 2007 Journal Headache Section Body Doc Link 17635594 Disease Relevance 0 Pain Relevance 0

Orally administered GTN is only active for 15 min in the rat or dog.

Positive_regulation (active) of GTN

9) Confidence 0.24 Published 1986 Journal Arzneimittelforschung Section Abstract Doc Link 3089233 Disease Relevance 0 Pain Relevance 0

The former decreased slightly in the TMP group but increased in the GTN and PGE(1) groups.

Positive_regulation (increased) of GTN

10) Confidence 0.24 Published 1991 Journal J Anesth Section Abstract Doc Link 15278629 Disease Relevance 0.15 Pain Relevance 0.08

Because decomposition of GTN by ALDH2 results in oxidation of the active site thiol that must subsequently be reduced to sustain catalysis, the proposed involvement of ALDH2 in the bioactivation of GTN revived the early proposal that ascribed nitrate tolerance to thiol depletion (34).

Positive_regulation (bioactivation) of GTN associated with tolerance

11) Confidence 0.22 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0.08 Pain Relevance 0.16

The “rapid” irreversible inactivation was exacerbated when the GTN concentration was increased, whereas the slower process was not affected.

Positive_regulation (increased) of GTN

12) Confidence 0.20 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2576553 Disease Relevance 0 Pain Relevance 0.04

The results on kinetics of inhibition by various inhibitors suggest that hematin may be an effective inhibitor to delineate the role of specific GST isozymes in the bioactivation of GTN.

Positive_regulation (bioactivation) of GTN

13) Confidence 0.16 Published 1996 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 8887455 Disease Relevance 0 Pain Relevance 0

Because GSTs are multifunctional enzymes and a multitude of GST isozymes with varying substrate preferences are present in mammalian tissues, the role of specific GST isozymes in bioactivation of GTN in rabbit aorta needs to be established.

Positive_regulation (bioactivation) of GTN in aorta

14) Confidence 0.16 Published 1996 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 8887455 Disease Relevance 0.08 Pain Relevance 0.08

This may reflect low affinity of ALDH2*2 for GTN rather than for NAD, because GTN reductase activity is only moderately increased by the coenzyme (Fig. 5).

Positive_regulation (increased) of GTN

15) Confidence 0.13 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

In addition, our data revealed an unexpected discrepancy between GTN reductase activity and sGC activation, suggesting that GTN denitration and bioactivation may reflect independent pathways of ALDH2-catalyzed GTN biotransformation.

Positive_regulation (activation) of GTN

16) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0.04

Immunoblot analysis indicated that the majority of vascular ALDH2 is present in the cytoplasm, suggesting that mitochondrial biotransformation of GTN by ALDH2 plays a minor role in the overall vascular biotransformation of GTN by this enzyme.

Positive_regulation (biotransformation) of GTN

17) Confidence 0.12 Published 2003 Journal Mol. Pharmacol. Section Abstract Doc Link 14573760 Disease Relevance 0.26 Pain Relevance 0.11

Tolerance to GTN was induced using both in vivo and in vitro protocols.

Positive_regulation (induced) of GTN associated with tolerance

18) Confidence 0.12 Published 2003 Journal Mol. Pharmacol. Section Abstract Doc Link 14573760 Disease Relevance 0.20 Pain Relevance 0.30

Bioactivation of GTN was assayed by coincubation of ALDH2 with purified sGC and determination of GTN-induced cGMP formation.

Positive_regulation (Bioactivation) of GTN

19) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

The effect of the E487K substitution on GTN reductase activity decreased with increasing GTN concentration (3 and 15% of wild type with 2 and 100 ?

Positive_regulation (increasing) of GTN

20) Confidence 0.12 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2801295 Disease Relevance 0 Pain Relevance 0

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