INT29105

Context Info Confidence 0.70 First Reported 1985 Last Reported 2010 Negated 1 Speculated 3 Reported most in Abstract Documents 68 Total Number 71 Disease Relevance 7.06 Pain Relevance 44.69

plasma membrane (OPRK1) signal transducer activity (OPRK1)

Anatomy Link Frequency brain 2 ICB 2 spinal 2 heart 2 plasma 1 OPRK1 (Homo sapiens)

Pain Link Frequency Relevance Heat Kappa opioid receptor 229 100.00 agonist 134 100.00 Opioid 118 100.00 Dynorphin 57 100.00 opiate 22 100.00 Enkephalin 19 100.00 Spinal cord 15 100.00 Analgesic 14 100.00 cocaine 49 99.98 antagonist 59 99.96

Disease Link Frequency Relevance Heat Bordatella Infection 13 99.64 Opiate Addiction 17 99.58 Respiratory Tract Infection 6 99.00 Disease 14 98.88 Adhesions 6 98.84 Pruritus 83 97.80 Increased Venous Pressure Under Development 5 97.64 Stress 1 97.64 Alcohol Addiction 4 97.08 Overactive Bladder 1 95.76

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Preclinical studies suggest that visceral afferents constitutively express kappa-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation.

Positive_regulation (activation) of KOR in visceral associated with kappa opioid receptor

1) Confidence 0.70 Published 2003 Journal Pain Section Abstract Doc Link 12507703 Disease Relevance 0.58 Pain Relevance 0.90

These findings are consistent with complex consequences of KOR activation in the spinal cord.

Positive_regulation (activation) of KOR in spinal cord associated with spinal cord

2) Confidence 0.69 Published 2004 Journal Neuroscience Section Abstract Doc Link 15026128 Disease Relevance 0 Pain Relevance 0.33

These findings demonstrate for the first time that kappa2 receptor numbers are upregulated by cocaine exposure.

Positive_regulation (upregulated) of kappa2 receptor associated with cocaine

3) Confidence 0.69 Published 1997 Journal J. Neurosci. Section Abstract Doc Link 9334398 Disease Relevance 0.36 Pain Relevance 0.58

These results suggest that select opioid ligands up-regulate rKOR by enhancing the rate of receptor folding and maturation and by protecting the receptor from degradation, resulting in an increase in the number of rKOR binding sites, immunoreactive protein, and functional receptors.

Positive_regulation (increase) of rKOR associated with opioid

4) Confidence 0.68 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 17720886 Disease Relevance 0 Pain Relevance 0.30

KOR activation by its endogenous ligand dynorphin A(1-17) decreases basal and drug-induced striatal levels of dopamine.

Positive_regulation (activation) of KOR associated with dopamine, dynorphin and kappa opioid receptor

5) Confidence 0.65 Published 2004 Journal Pharmacogenetics Section Abstract Doc Link 15608558 Disease Relevance 0.24 Pain Relevance 0.67

Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms.

Positive_regulation (activate) of kappa-opiate receptor in spinal associated with nociceptor, analgesic and opiate

6) Confidence 0.59 Published 1996 Journal Pain Section Title Doc Link 8783328 Disease Relevance 0 Pain Relevance 1.42

This indicates that exposure (of non-pregnant animals) to the pregnancy blood profile of E2 and P activates a spinal cord kappa-opiate receptor analgesic system, as occurs during actual gestation.

Positive_regulation (activates) of kappa-opiate receptor in blood associated with analgesic, opiate and spinal cord

7) Confidence 0.59 Published 1996 Journal Pain Section Abstract Doc Link 8783328 Disease Relevance 0 Pain Relevance 1.51

A select set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat kappa-opioid receptor in human embryonic kidney 293 cells.

Positive_regulation (promoting) of kappa-opioid receptor in embryonic kidney associated with narcan, kappa opioid receptor and opioid

8) Confidence 0.59 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 17720886 Disease Relevance 0 Pain Relevance 0.43

Emphasis will be placed on demonstration of a rodent model in which butorphanol administration induces dependence through a unique (in comparison with morphine) activation of the kappa-opioid receptor.

Positive_regulation (activation) of kappa-opioid receptor associated with addiction, kappa opioid receptor, butorphanol and morphine

9) Confidence 0.57 Published 1997 Journal Nihon Shinkei Seishin Yakurigaku Zasshi Section Abstract Doc Link 9365966 Disease Relevance 0.29 Pain Relevance 1.75

Pan discusses the accumulating evidence that activation of the kappa-receptor antagonizes various mu-receptor-mediated actions in the brain, including analgesia, tolerance, reward and memory processes.

Positive_regulation (activation) of kappa-receptor in brain associated with tolerance and analgesia

10) Confidence 0.54 Published 1998 Journal Trends Pharmacol. Sci. Section Abstract Doc Link 9584625 Disease Relevance 0 Pain Relevance 0.66

Various parameters governing the arterial baroreflex control of heart rate were assessed before and after activation of kappa-opiate receptors (KOR) by i.v. administration of the specific KOR agonist U-50488H (experiment 1) or vehicle (experiment 2) to conscious, chronically instrumented lambs aged 42 +/- 2 days (n = 6).

Positive_regulation (activation) of KOR in heart associated with agonist and opiate

11) Confidence 0.49 Published 2007 Journal Can. J. Physiol. Pharmacol. Section Abstract Doc Link 17901891 Disease Relevance 0 Pain Relevance 0.32

These results suggest that select opioid ligands up-regulate rKOR by enhancing the rate of receptor folding and maturation and by protecting the receptor from degradation, resulting in an increase in the number of rKOR binding sites, immunoreactive protein, and functional receptors.

Positive_regulation (up-regulate) of rKOR associated with opioid

12) Confidence 0.45 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 17720886 Disease Relevance 0 Pain Relevance 0.31

CONCLUSIONS: Our results demonstrate that expression of three types of ORs, MOR, DOR and KOR, was markedly upregulated in human hypertrophic scars, suggesting a possible link between upregulated ORs and local cacaesthesia in hypertrophic scars.

Positive_regulation (upregulated) of KOR

13) Confidence 0.45 Published 2008 Journal Br. J. Dermatol. Section Body Doc Link 18284397 Disease Relevance 0.05 Pain Relevance 0

Thus, the high affinity that buprenorphine has for the kappa receptor results in potent kappa receptor antagonist activity in vivo.

Positive_regulation (results) of kappa receptor associated with antagonist and buprenorphine

14) Confidence 0.45 Published 1987 Journal Neuropharmacology Section Abstract Doc Link 2823167 Disease Relevance 0.10 Pain Relevance 0.71

Related studies focused on full-length cloning of the coding region of the rhesus monkey kappa-opioid receptor (OPRK1) gene and revealed a high homology of the nonhuman primate OPRK1 gene compared with the human OPRK1 gene, including particular C-terminal residues thought to be involved in receptor desensitization and internalization.

Positive_regulation (homology) of OPRK1 associated with kappa opioid receptor

15) Confidence 0.44 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 17060493 Disease Relevance 0 Pain Relevance 0.40

In addition, the presence of increased KOR density and proportionally elevated intracellular KORs in proestrus/estrus females suggests a basis for sex-linked differences in KOR-mediated antinociception.

Positive_regulation (increased) of KOR associated with antinociception and kappa opioid receptor

16) Confidence 0.44 Published 2004 Journal Neuroscience Section Abstract Doc Link 15026128 Disease Relevance 0 Pain Relevance 0.34

The data confirm the participation of glutamate as a general phenomenon in opioid dependence, identify the locus coeruleus as a primary site for glutamatergic mediation of dependence, and suggest novel aspects to the neuropharmacology of opioid dependence with respect to the role of the kappa-opioid receptor.

Positive_regulation (role) of kappa-opioid receptor in locus coeruleus associated with addiction, glutamate, locus ceruleus, kappa opioid receptor and opioid

17) Confidence 0.41 Published 1997 Journal Nihon Shinkei Seishin Yakurigaku Zasshi Section Abstract Doc Link 9365966 Disease Relevance 0.35 Pain Relevance 1.58

Brefeldin A caused accumulation of intracellular rKOR intermediates, and coincubation with naltrexone increased the levels of the brefeldin-induced species significantly.

Positive_regulation (accumulation) of rKOR

18) Confidence 0.40 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 17720886 Disease Relevance 0 Pain Relevance 0.34

Naltrexone did not alter rKOR mRNA levels or translational efficiency, and rKOR up-regulation was not inhibited by cycloheximide.

Neg (not) Positive_regulation (up-regulation) of rKOR

19) Confidence 0.40 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 17720886 Disease Relevance 0 Pain Relevance 0.34

The present study further demonstrates that the KOR of lymphocytes are activated in the presence of extracellular morphine or U50,488H, a KOR selective agonist, and the activation causes an increase in the expression of KOR mRNA, as determined by a quantitative competitive Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) procedure.

Positive_regulation (activated) of KOR in lymphocytes associated with agonist, kappa opioid receptor and morphine

20) Confidence 0.38 Published 2001 Journal Int. Immunopharmacol. Section Abstract Doc Link 11562065 Disease Relevance 0 Pain Relevance 0.83

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