INT224234

Context Info Confidence 0.65 First Reported 2007 Last Reported 2010 Negated 0 Speculated 3 Reported most in Body Documents 33 Total Number 36 Disease Relevance 4.25 Pain Relevance 3.45

plasma membrane (GPR17) signal transducer activity (GPR17)

Anatomy Link Frequency brain 12 heart 7 kidney 3 1321N1 2 hypothalamus 1 GPR17 (Homo sapiens)

Pain Link Frequency Relevance Heat Glutamate 170 99.98 Hippocampus 192 99.92 Dopamine 114 99.68 Spinal cord 65 99.38 agonist 256 95.36 amygdala 96 95.32 Thalamus 96 94.92 Neurotransmitter 77 92.64 Serotonin 9 63.92 Cannabinoid receptor 32 53.28

Disease Link Frequency Relevance Heat Urological Neuroanatomy 128 100.00 Frailty 64 99.52 Anaplastic Astrocytoma 64 99.12 Cancer 72 97.60 Targeted Disruption 96 97.52 Cv Unclassified Under Development 64 96.04 Bordatella Infection 224 91.64 Osteoporosis 40 56.48 Appetite Loss 32 6.36 Hypoxia 103 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

This can be followed by norepinephrine and epinephrine syntheses (r128–r129).

Gene_expression (syntheses) of r12

1) Confidence 0.65 Published 2007 Journal Theor Biol Med Model Section Body Doc Link PMC2246127 Disease Relevance 0 Pain Relevance 0.39

This can be followed by norepinephrine and epinephrine syntheses (r128–r129).

Gene_expression (syntheses) of r12

2) Confidence 0.65 Published 2007 Journal Theor Biol Med Model Section Body Doc Link PMC2246127 Disease Relevance 0 Pain Relevance 0.39

Hence, lysine was allowed to be taken up by neurons leading to glutamate production (r120–r121) and it was degraded to acetyl-CoA (r122–r124) [68,72].

Gene_expression (production) of r12 in neurons associated with glutamate

3) Confidence 0.65 Published 2007 Journal Theor Biol Med Model Section Body Doc Link PMC2246127 Disease Relevance 0 Pain Relevance 0.13

Earlier studies of GPR17 gene expression in humans, rats and mice have shown that the receptor is primarily expressed in brain.

Gene_expression (expression) of GPR17 gene in brain

4) Confidence 0.10 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.07 Pain Relevance 0

It was furthermore shown that GPR17 expression was up-regulated in a rat model of ischaemic damage and that knock-down of the receptor prevented ischaemia, suggesting that GPR17 putatively could function as a mediator of brain damage (Ciana et al., 2006).

Gene_expression (expression) of GPR17 in brain associated with targeted disruption and cv unclassified under development

5) Confidence 0.10 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.34 Pain Relevance 0.08

Isoform-specific analysis of GPR17 gene expression in brain, heart and kidneys

Gene_expression (expression) of GPR17 gene in heart

6) Confidence 0.10 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.07 Pain Relevance 0

In order to obtain a more detailed picture of the expression pattern, using quantitative RT-PCR, we determined the relative expression levels of the two GPR17 isoforms in eight different brain regions as well as whole brain, heart and kidney.

Spec (determined) Gene_expression (expression) of GPR17 in kidney

7) Confidence 0.10 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.05 Pain Relevance 0

As hGPR17-S mainly is expressed in the brain, [35S]-GTP?

Gene_expression (expressed) of hGPR17 in brain

8) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.23 Pain Relevance 0

-actin and presented relative to the normalized hGPR17-L expression in whole brain.

Gene_expression (expression) of hGPR17 in brain

9) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.13 Pain Relevance 0.17

Expression levels of the hGPR17 isoforms were determined in several brain regions as well as heart and kidney using quantitative RT-PCR.

Gene_expression (Expression) of hGPR17 in kidney

10) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Abstract Doc Link PMC2839267 Disease Relevance 0 Pain Relevance 0

Both isoforms were expressed well with hGPR17-S being present at approximately 30–40% higher levels than hGPR17-L at corresponding doses (Figure 3D).

Gene_expression (expressed) of hGPR17

11) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.05 Pain Relevance 0

Thus, in the heart, hGPR17-L was expressed at approximately 12-fold higher levels than hGPR17-S.

Gene_expression (expressed) of hGPR17 in heart

12) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.07 Pain Relevance 0.13

Given the absence of hGPR17-S expression in kidneys, the similar comparison was not applicable for this organ (Figure 2C, right).

Gene_expression (expression) of hGPR17

13) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.07 Pain Relevance 0.12

In both tissues, hGPR17-L was expressed at higher levels compared with total brain (approximately seven- and twofold respectively), while the opposite was the case for hGPR17-S.

Gene_expression (expressed) of hGPR17 in brain

14) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.14 Pain Relevance 0.20

i-coupled receptors (such as GPR17) compared with G?

Gene_expression (compared) of GPR17

15) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0 Pain Relevance 0

Different functional properties of GPR17 isoforms

Gene_expression (isoforms) of GPR17

16) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0 Pain Relevance 0.06

The cellular localization of the construct was evaluated using confocal microscopy in HEK293 cells and, as GPR17 is mainly expressed in the brain, 1321N1 astrocytoma cells.

Gene_expression (expressed) of GPR17 in 1321N1 associated with anaplastic astrocytoma

17) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.10 Pain Relevance 0

Notably, in two rodent models of ischaemic damage (Ciana et al., 2006; Lecca et al., 2008) and a model of spinal cord injury (Ceruti et al., 2009), GPR17 expression is up-regulated.

Gene_expression (expression) of GPR17 in spinal cord associated with spinal cord

18) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.10 Pain Relevance 0.18

In the present study, we carry out a detailed expression analysis of the two human GPR17 isoforms in a range of brain regions as well as the heart and kidney.

Gene_expression (expression) of GPR17 in brain

19) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.40 Pain Relevance 0.07

Thus, in whole brain, hGPR17-S was expressed at approximately 10-fold higher levels than hGPR17-L, which was also observed in hypothalamus, cerebellar hemisphere and frontal cortex.

Gene_expression (expressed) of hGPR17 in hypothalamus associated with urological neuroanatomy

20) Confidence 0.07 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2839267 Disease Relevance 0.25 Pain Relevance 0.28

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