INT158270

Context Info Confidence 0.57 First Reported 2009 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 10 Total Number 10 Disease Relevance 2.49 Pain Relevance 0.52

transport (Trpm5) plasma membrane (Trpm5) biological_process (Trpm5)

Anatomy Link Frequency noses 1 Trpm5 (Mus musculus)

Pain Link Frequency Relevance Heat qutenza 74 90.24 imagery 147 86.24 TRP channel 19 69.88 fifth nerve 14 40.96 substance P 36 31.44 addiction 12 5.00 Inflammation 7 5.00 Neurotransmitter 6 5.00 Potency 6 5.00 Central nervous system 1 5.00

Disease Link Frequency Relevance Heat Targeted Disruption 147 99.96 Taste Disorders 3 66.24 Aging 6 54.24 Dislocations 6 36.16 INFLAMMATION 7 5.00 Body Weight 7 5.00 Loss Of Sense Of Smell 4 5.00 Death 3 5.00 Brain Injury 2 5.00 Apoptosis 2 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Unlike the TRPM5 inhibitor, U73122 also disrupted the regulation on the access of lilial in both wild type and TRPM5 knockout mice.

Negative_regulation (inhibitor) of TRPM5 associated with targeted disruption

1) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912856 Disease Relevance 0.56 Pain Relevance 0.04

Application of TRPM5 inhibitor produced similar effect.

Negative_regulation (inhibitor) of TRPM5

2) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912856 Disease Relevance 0.46 Pain Relevance 0

Genetic knockout and pharmacological inhibition of TRPM5 resulted in larger amounts of bitter compounds entering the VNOs.

Negative_regulation (inhibition) of TRPM5 associated with targeted disruption

3) Confidence 0.42 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2912856 Disease Relevance 0.16 Pain Relevance 0.08

Further, we determined sensory signaling transduction mechanisms using both TRPM5 knockout mice and inhibitors to block the activity of TRPM5 and PLC.

Negative_regulation (block) of TRPM5 associated with targeted disruption

4) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912856 Disease Relevance 0.10 Pain Relevance 0

In contrast, MgSO(4) and CuSO(4) were aversive to WT mice, but for MgSO(4) the aversion was abolished in TRPM5 knock-out animals, and for CuSO(4), aversion decreased in both TRPV1- and TRPM5-deficient animals.

Negative_regulation (abolished) of TRPM5 associated with targeted disruption

5) Confidence 0.42 Published 2009 Journal J. Neurosci. Section Abstract Doc Link 19244541 Disease Relevance 0.26 Pain Relevance 0.12

In contrast, MgSO(4) and CuSO(4) were aversive to WT mice, but for MgSO(4) the aversion was abolished in TRPM5 knock-out animals, and for CuSO(4), aversion decreased in both TRPV1- and TRPM5-deficient animals.

Negative_regulation (decreased) of TRPM5 associated with targeted disruption

6) Confidence 0.42 Published 2009 Journal J. Neurosci. Section Abstract Doc Link 19244541 Disease Relevance 0.26 Pain Relevance 0.12

Similar to the TRPM5 inhibitor, application of the PLC inhibitor U73122 also disrupted the regulation on access to the VNO of bitter compounds in wild type but not in TRPM5 knockout mice.

Negative_regulation (inhibitor) of TRPM5 associated with targeted disruption

7) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912856 Disease Relevance 0.50 Pain Relevance 0.04

TRPM5 inhibitors Ph3PO (100 µM) and PLC inhibitor U73122 (10 µM) respectively were delivered to the noses of individual animals using the same method described in stimulus delivery.

Negative_regulation (inhibitors) of TRPM5 in noses

8) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2912856 Disease Relevance 0 Pain Relevance 0

Distribution of TRPV1-4, TRPM5, TRPM8, and TRPA1 in mouse OE

Negative_regulation (Distribution) of TRPM5

9) Confidence 0.41 Published 2010 Journal Acta Oto-Laryngologica Section Body Doc Link PMC2981077 Disease Relevance 0 Pain Relevance 0

At low concentrations, FeSO(4) and ZnSO(4) were perceived as pleasant stimuli by WT mice, and this effect was fully reversed in TRPM5 knock-out mice.

Negative_regulation (reversed) of TRPM5 associated with targeted disruption

10) Confidence 0.36 Published 2009 Journal J. Neurosci. Section Abstract Doc Link 19244541 Disease Relevance 0.19 Pain Relevance 0.12

General Comments

This test has worked.