INT15995

Context Info Confidence 0.49 First Reported 1986 Last Reported 2010 Negated 3 Speculated 0 Reported most in Abstract Documents 18 Total Number 18 Disease Relevance 3.94 Pain Relevance 4.63

cytosol (Alox5) nuclear envelope (Alox5) oxidoreductase activity (Alox5) nucleus (Alox5) cytoplasm (Alox5)

Anatomy Link Frequency sensory neurons 2 smooth muscle 2 neuronal 1 cerebral cortex 1 mast cells 1 Alox5 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Kinase C 4 100.00 5HT 10 99.16 cerebral cortex 1 99.10 Thermal hyperalgesia 15 99.02 cINOD 8 98.44 antagonist 14 97.24 Glutamate 2 96.14 nMDA receptor 5 94.72 Glutamate receptor 1 94.28 substantia gelatinosa 6 92.72

Disease Link Frequency Relevance Heat Hyperalgesia 18 99.02 Leukemia 1 98.80 INFLAMMATION 35 97.44 Respiratory Syncytial Virus 8 97.36 Breast Cancer 1 96.08 Pain 3 89.44 Hepatotoxicity 10 86.20 Injury 12 85.92 Ganglion Cysts 2 83.32 Cirrhosis 1 78.68

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Increased concentrations of 5-lipoxygenase-encoding mRNA and cysLTs, as well as numerous mast cells, were detected in the lung tissues of RSV-infected weanling rats.

Positive_regulation (Increased) of 5-lipoxygenase in mast cells associated with respiratory syncytial virus

1) Confidence 0.49 Published 2002 Journal Am. J. Physiol. Lung Cell Mol. Physiol. Section Abstract Doc Link 11943681 Disease Relevance 0.77 Pain Relevance 0.33

Lipoxygenase activation is not found with other topical irritants or nonsteroidal anti-inflammatory drugs.

Positive_regulation (activation) of Lipoxygenase associated with inflammation and cinod

2) Confidence 0.44 Published 1991 Journal J. Physiol. Pharmacol. Section Abstract Doc Link 1782414 Disease Relevance 0.15 Pain Relevance 0.15

We thus conclude that histamine activates TRPV1 after stimulating the PLA(2)/LO pathway, leading to the excitation of sensory neurons.

Positive_regulation (leading) of LO in sensory neurons

3) Confidence 0.43 Published 2004 Journal Neurosci. Lett. Section Abstract Doc Link 15135918 Disease Relevance 0.14 Pain Relevance 0.23

We thus conclude that histamine activates TRPV1 after stimulating the PLA(2)/LO pathway, leading to the excitation of sensory neurons.

Positive_regulation (stimulating) of LO in sensory neurons

4) Confidence 0.43 Published 2004 Journal Neurosci. Lett. Section Abstract Doc Link 15135918 Disease Relevance 0.15 Pain Relevance 0.23

Cellular 5-LOX activation was obtained by adding calcium ionophore (A23187) into the pouch thus providing a novel model to evaluate the efficacy and selectivity of 5-LOX inhibitors.

Positive_regulation (activation) of 5-LOX

5) Confidence 0.40 Published 2008 Journal Eur. J. Pharmacol. Section Abstract Doc Link 18295198 Disease Relevance 0.71 Pain Relevance 0.24

CONCLUSION: S-ropivacaine induces dose-dependent biphasic contractions in rat aortic smooth muscle through a mechanism requiring extracellular calcium that is mediated by activation of the lipoxygenase pathway and, to a lesser extent, the cyclooxygenase pathway.

Positive_regulation (activation) of lipoxygenase in smooth muscle

6) Confidence 0.38 Published 2009 Journal Can J Anaesth Section Body Doc Link 19296191 Disease Relevance 0 Pain Relevance 0

To investigate the hypothesis that the gastric damage caused by NSAIDs is due not only to the decreased level of cyclooxygenase products but to the increased level of lipoxygenase products as well, different lipoxygenase inhibitors and leukotriene antagonists were tested.

Positive_regulation (increased) of lipoxygenase associated with antagonist and cinod

7) Confidence 0.38 Published 1993 Journal Arzneimittelforschung Section Abstract Doc Link 8369011 Disease Relevance 0.22 Pain Relevance 0.35

Lipoxygenase (LO) metabolites are generated in inflamed tissues.

Positive_regulation (generated) of Lipoxygenase

8) Confidence 0.37 Published 2009 Journal Mol. Cells Section Abstract Doc Link 19390822 Disease Relevance 0.25 Pain Relevance 0.28

CONCLUSIONS: Our data indicate that levobupivacaine-induced contraction of rat aortic smooth muscle is mediated mainly by activation of the lipoxygenase pathway and in part by activation of the cyclooxygenase pathway.

Positive_regulation (activation) of lipoxygenase in smooth muscle

9) Confidence 0.34 Published 2010 Journal Anesth. Analg. Section Body Doc Link 19955508 Disease Relevance 0 Pain Relevance 0

In addition, activation of the lipoxygenase pathway seems to facilitate calcium influx via L-type calcium channels.

Positive_regulation (activation) of lipoxygenase

10) Confidence 0.34 Published 2010 Journal Anesth. Analg. Section Body Doc Link 19955508 Disease Relevance 0 Pain Relevance 0

Lipoxygenase (LO) metabolites are generated in inflamed tissues.

Positive_regulation (generated) of LO

11) Confidence 0.32 Published 2009 Journal Mol. Cells Section Abstract Doc Link 19390822 Disease Relevance 0.25 Pain Relevance 0.28

The former action is mediated by glutamate-receptor activation and neuronal activity increase, possibly the facilitatory effect of PLA(2) activation on excitatory transmission, whereas the latter action is due to PLA(2) and subsequent lipoxygenase activation and is independent of extracellular Ca(2+).

Positive_regulation (activation) of lipoxygenase in neuronal associated with glutamate

12) Confidence 0.22 Published 2008 Journal J. Neurophysiol. Section Abstract Doc Link 18216222 Disease Relevance 0 Pain Relevance 0.47

In the present study we show that neither indomethacin nor BW 755C inhibits 5HT stimulated phosphoinositide hydrolysis in rat cerebral cortex, suggesting that neither cyclooxygenase nor lipoxygenase activity is required for the response to 5HT.

Neg (neither) Positive_regulation (required) of lipoxygenase in cerebral cortex associated with 5ht and cerebral cortex

13) Confidence 0.19 Published 1986 Journal Life Sci. Section Abstract Doc Link 3003490 Disease Relevance 0 Pain Relevance 0.77

The treatment with Fad had no effect on the expression of MMP-1 mRNA and increased that of LO mRNA.

Neg (no) Positive_regulation (increased) of LO mRNA

14) Confidence 0.17 Published 2004 Journal J. Endocrinol. Section Abstract Doc Link 14765986 Disease Relevance 0.24 Pain Relevance 0.12

The thermal hyperalgesia produced by N-methyl-D-aspartate is mediated by activation of nitric oxide synthase and protein kinase C, but not by phospholipase C, phospholipase A2, cyclo-oxygenase or lipoxygenase.

Positive_regulation (activation) of lipoxygenase associated with kinase c and thermal hyperalgesia

15) Confidence 0.04 Published 1996 Journal Neuroscience Section Abstract Doc Link 9053788 Disease Relevance 0.63 Pain Relevance 1.12

In summary, defined natural tetracyclic triterpenes, which act as inhibitors of the 5-LO in the cell-free assay, initiate 5-LO activation by a MEK-inhibitor sensitive mechanism and potentiate stimulated product synthesis in intact cells.

Positive_regulation (activation) of 5-LO

16) Confidence 0.03 Published 2001 Journal Mol. Pharmacol. Section Abstract Doc Link 11455013 Disease Relevance 0 Pain Relevance 0

Steroid-type tetracycles neither induced 5-LO activation nor had enhancing or inhibitory effects.

Neg (neither) Positive_regulation (activation) of 5-LO

17) Confidence 0.03 Published 2001 Journal Mol. Pharmacol. Section Abstract Doc Link 11455013 Disease Relevance 0 Pain Relevance 0

required phospholipase A2 and lipoxygenase activity with subsequent release of arachidonic acid metabolites [32].

Positive_regulation (required) of lipoxygenase

18) Confidence 0.01 Published 2010 Journal International Journal of Molecular Sciences Section Body Doc Link PMC3000109 Disease Relevance 0.43 Pain Relevance 0.04

General Comments

This test has worked.