INT11624

Context Info Confidence 0.78 First Reported 1982 Last Reported 2010 Negated 8 Speculated 10 Reported most in Body Documents 445 Total Number 456 Disease Relevance 72.36 Pain Relevance 294.36

Golgi apparatus (OPRM1) endoplasmic reticulum (OPRM1) plasma membrane (OPRM1) signal transducer activity (OPRM1)

Anatomy Link Frequency neurons 17 embryonic kidney 17 epidermis 11 brain 10 ganglia 10 OPRM1 (Homo sapiens) OPRM1 - A118G (1) OPRM1 - S268P (1)

Pain Link Frequency Relevance Heat opioid receptor 8439 100.00 Morphine 5358 100.00 Opioid 3213 100.00 agonist 2722 100.00 narcan 1873 100.00 mu opioid receptor 1593 100.00 antagonist 1394 100.00 tolerance 853 100.00 analgesia 467 100.00 opiate 415 100.00

Disease Link Frequency Relevance Heat Targeted Disruption 29 100.00 Neuroblastoma 254 99.96 Pheochromocytoma 104 99.96 Nociception 630 99.92 INFLAMMATION 1346 99.88 Repression 8 99.84 Pain 507 99.76 Acquired Immune Deficiency Syndrome Or Hiv Infection 112 99.76 Infection 66 99.76 Chronic Fatigue Syndrome 14 99.72

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

MOR expression is regulated at the transcriptional and post-transcriptional levels.

Gene_expression (expression) of MOR associated with mu opioid receptor

1) Confidence 0.78 Published 2010 Journal J. Cell. Mol. Med. Section Abstract Doc Link 19438807 Disease Relevance 0 Pain Relevance 0.51

These results indicate that re-initiation in MOR gene expression could play an important role in OPRM1 regulation.

Gene_expression (expression) of MOR gene associated with mu opioid receptor

2) Confidence 0.78 Published 2010 Journal J. Cell. Mol. Med. Section Abstract Doc Link 19438807 Disease Relevance 0 Pain Relevance 0.40

However, the protein expression of the MOR gene is relatively low and the translational control of MOR gene has not been well studied.

Gene_expression (expression) of MOR gene associated with mu opioid receptor

3) Confidence 0.78 Published 2010 Journal J. Cell. Mol. Med. Section Abstract Doc Link 19438807 Disease Relevance 0 Pain Relevance 0.51

The data suggest that MOP expression is controlled in part by initiation of the long form of MOP at the alternate site.

Gene_expression (expression) of MOP

4) Confidence 0.78 Published 2009 Journal Cell. Mol. Life Sci. Section Abstract Doc Link 19609488 Disease Relevance 0 Pain Relevance 0.20

As the highest relative expression levels are in transformed neuronal cell lines, MOR1K expression is likely to be suppressed in native cellular conditions.

Gene_expression (expression) of MOR1K in neuronal

5) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.49 Pain Relevance 0.45

MOR1K expression was not observed in the connective tissue surrounding DRG or in peripheral leukocytes.

Gene_expression (expression) of MOR1K in DRG associated with dorsal root ganglion

6) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.51 Pain Relevance 0.56

To test this hypothesis, we first characterized tissue-specific expression levels of MOR1K, its cellular localization, and agonist binding capacity to confirm potential functionality of this new receptor isoform.

Gene_expression (expression) of MOR1K associated with agonist

7) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.15 Pain Relevance 0.55

Additionally, MOR1K was expressed at high levels in the human neuroblastoma cell lines Be2C and SH-SY5Y, while no expression was observed in monkey kidney COS-1 and human astrocytoma H4 cell lines.

Neg (no) Gene_expression (expressed) of MOR1K in SH-SY5Y associated with anaplastic astrocytoma and neuroblastoma

8) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.47 Pain Relevance 0.50

Overexpression of MOR1K in mammalian cells revealed that this 6TM receptor is not expressed at the cell membrane, but instead is retained in the intracellular compartment (Fig.1C).

Gene_expression (Overexpression) of MOR1K

9) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.40 Pain Relevance 0.41

For the cAMP accumulation assay, MOR1 or MOR1K expressants were plated on 12 well plates and grown to 90% confluency.

Gene_expression (expressants) of MOR1K

10) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0 Pain Relevance 0.15

These brain regions are known to also express MOR1 and contribute to the pharmacological effects of MOR agonists.

Gene_expression (express) of MOR1 in brain associated with agonist and opioid receptor

11) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.50 Pain Relevance 0.64

Genetic analyses revealed that allelic variants coding for higher MOR1K expression are associated with greater sensitivity to noxious stimuli and blunted responses to morphine[32].

Gene_expression (expression) of MOR1K associated with morphine

12) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.15 Pain Relevance 0.63

Results from RT-PCR revealed that MOR1K is expressed in the frontal lobe, medulla oblongata, insula, nucleus accumbens, pons, spinal cord, and dorsal root ganglion (DRG) (Fig.1A-B).

Gene_expression (expressed) of MOR1K in lobe associated with ganglion cysts, dorsal root ganglion, nucleus accumbens, medulla, insula and spinal cord

13) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.46 Pain Relevance 0.70

A moderate increase in morphine-evoked Ca2+ levels was also observed in Be2C cells transfected with MOR1 or empty vector, however this was likely due to the high endogenous expression of MOR1K in this cell line (Fig.1B).

Gene_expression (expression) of MOR1K associated with morphine

14) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.16 Pain Relevance 0.93

For the cAMP accumulation assay, MOR1 or MOR1K expressants were plated on 12 well plates and grown to 90% confluency.

Gene_expression (expressants) of MOR1

15) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0 Pain Relevance 0.15

For MOR1 expressing cells, maximum NO production (7.5 pM) occurred at ~50 sec after administration of 1 ?

Gene_expression (expressing) of MOR1

16) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.08 Pain Relevance 1.23

A moderate increase in morphine-evoked Ca2+ levels was also observed in Be2C cells transfected with MOR1 or empty vector, however this was likely due to the high endogenous expression of MOR1K in this cell line (Fig.1B).

Gene_expression (transfected) of MOR1 associated with morphine

17) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.17 Pain Relevance 0.87

First, we characterized the relative expression of MOR1K in human brain and spinal cord as well as peripheral leukocytes using real-time PCR (RT-PCR).

Gene_expression (expression) of MOR1K in leukocytes associated with spinal cord

18) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.35 Pain Relevance 0.66

These data suggest that human MOR1K expression is restricted to neuronal cells.

Gene_expression (expression) of MOR1K in neuronal

19) Confidence 0.78 Published 2010 Journal Mol Pain Section Body Doc Link PMC2894766 Disease Relevance 0.50 Pain Relevance 0.46

Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain.

Gene_expression (expressed) of MOR in brain associated with inflammation and mu opioid receptor

20) Confidence 0.78 Published 1997 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 9152411 Disease Relevance 0.17 Pain Relevance 0.65

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