INT36039

Context Info Confidence 0.72 First Reported 1987 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 19 Total Number 22 Disease Relevance 3.75 Pain Relevance 2.93

nucleoplasm (Itpr3) transport (Itpr3) endoplasmic reticulum (Itpr3) nucleolus (Itpr3) nucleus (Itpr3) transmembrane transport (Itpr3)

Anatomy Link Frequency papillae 3 reticulum 2 Hyp3 1 platelets 1 taste buds 1 Itpr3 (Mus musculus)

Pain Link Frequency Relevance Heat Kinase C 7 100.00 agonist 131 98.76 bradykinin 22 98.72 Enkephalin 2 98.64 Antinociceptive 1 97.96 Pain threshold 3 97.44 Opioid 2 96.80 antagonist 21 95.44 member 8 20 94.12 Analgesic 2 87.56

Disease Link Frequency Relevance Heat Pain 5 97.44 Apoptosis 138 94.64 Brain Hemorrhage 32 87.76 Cv General 4 Under Development 12 86.72 Death 71 84.00 Bordatella Infection 2 81.36 Muscular Atrophy 1 80.48 Contracture 1 79.68 Syndrome 2 77.52 Disease 152 76.92

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

As expected, the results showed that almost all Lrmp/Jaw1-expressing taste cells also expressed IP3R3 in CV papillae (Figure 3).

Gene_expression (expressed) of IP3R3 in papillae

1) Confidence 0.72 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

Lrmp/Jaw1 was coexpressed with IP3R3

Gene_expression (coexpressed) of IP3R3

2) Confidence 0.72 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0.06 Pain Relevance 0

To investigate the coexpression patterns of Lrmp/Jaw1 and IP3R3 at the translational level, we performed double-colored immunohistochemistry using CV papillae sections.

Spec (investigate) Gene_expression (coexpression) of IP3R3 in papillae

3) Confidence 0.72 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

However, this is difficult to justify, at least for IP3R3 trafficking, because deletion of the potential binding domain (coiled-coil domain of Lrmp/Jaw1) did not alter IP3R3 expression on the ER membrane in the COS7 heterologous expression system.

Gene_expression (expression) of IP3R3

4) Confidence 0.72 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0.14 Pain Relevance 0

Because IP3R3 was coexpressed with Trpm5 in taste buds (Pérez et al. 2002), we predicted that Lrmp/Jaw1 may colocalize and interact with IP3R3.

Gene_expression (coexpressed) of IP3R3 in taste buds

5) Confidence 0.72 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

IP3(1,3,4) formed from inositol 1,3,4,5-tetrakisphosphate, which is itself a product of IP3(1,4,5), causes a slower depolarization by a mechanism that does not involve Na+ channels or an increase in [Ca++]i.

Gene_expression (product) of IP3

6) Confidence 0.67 Published 1988 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 3262737 Disease Relevance 0.07 Pain Relevance 0.06

Dibutyryl cyclic GMP produced little or no inhibition of IP3.

Gene_expression (produced) of IP3

7) Confidence 0.67 Published 1987 Journal J. Neurochem. Section Abstract Doc Link 3494104 Disease Relevance 0.23 Pain Relevance 0.62

2 to produce IP3, which induces calcium (Ca2+) release through IP3R3 located on the membrane of endoplasmic reticulum (ER).

Gene_expression (produce) of IP3 in reticulum

8) Confidence 0.63 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0.19

To investigate the coexpression patterns of Lrmp/Jaw1 and IP3R3 at the translational level, we performed double-colored immunohistochemistry using CV papillae sections.

Spec (investigate) Gene_expression (patterns) of IP3R3 in papillae

9) Confidence 0.56 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

In our study, we found that Lrmp/Jaw1, a gene encoding lymphoid-restricted membrane protein (Behrens et al. 1994; Hoon and Ryba 1997), was coexpressed with molecules in the IP3-Ca2+ signal cascade in taste cells.

Gene_expression (coexpressed) of IP3

10) Confidence 0.55 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

Pretreatment with D-myo inositol, compound which produces InsP3, and 4-chloro-m-cresol, a RyR agonist, induced an antinociceptive effect.

Gene_expression (produces) of InsP3 associated with agonist and antinociceptive

11) Confidence 0.50 Published 2004 Journal Neuropharmacology Section Abstract Doc Link 15527827 Disease Relevance 0.54 Pain Relevance 0.80

Coexpression of Lrmp/Jaw1 with the molecules related with IP3-Ca2+ signal cascade such as G?

Gene_expression (Coexpression) of IP3

12) Confidence 0.49 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

The expression plasmid of rat IP3R3 (Blondel et al. 1993) was kindly provided by Dr Graeme I.

Gene_expression (expression) of IP3R3

13) Confidence 0.49 Published 2010 Journal Chemical Senses Section Body Doc Link PMC2805811 Disease Relevance 0 Pain Relevance 0

In particular, [D-Arg0]-Hyp3-Thi5,8-[D-Phe7]-bradykinin [Hyp, hydroxyproline; Thi, beta-(2-thienyl)-L-alanine] blocked IP3 production in a dose-dependent fashion.

Gene_expression (production) of IP3 in Hyp3 associated with bradykinin

14) Confidence 0.45 Published 1987 Journal J. Neurochem. Section Abstract Doc Link 3494104 Disease Relevance 0.37 Pain Relevance 0.58

Although these agonists trigger different signaling pathways, all activate phospholipase Cs (PLCs), leading to the production of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3).

Gene_expression (production) of IP3 associated with agonist

15) Confidence 0.07 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2442636 Disease Relevance 0.71 Pain Relevance 0.08

2 stimulation (Fig. 2 A), suggesting different kinetics of IP3 production between these two pathways that could influence subsequent events.

Gene_expression (production) of IP3

16) Confidence 0.06 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2442636 Disease Relevance 0 Pain Relevance 0.16

M1 receptors are thought to couple to Gq/11 subunits whose downstream signaling bifurcates into the production of IP3 and DAG, leading to activation of PKC (Delmas and Brown, 2005).

Gene_expression (production) of IP3

17) Confidence 0.05 Published 2010 Journal Neuron Section Body Doc Link PMC3003154 Disease Relevance 0 Pain Relevance 0.03

, are viable with no obvious neurological defects, although they have some defects in fertility, decreased platelet levels (30%) of PI(4,5)P2 and impaired thrombin-induced IP3 production in platelets (45).

Gene_expression (production) of IP3 in platelets

18) Confidence 0.05 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2937898 Disease Relevance 0.37 Pain Relevance 0

Gq/11 subunits' downstream signaling bifurcates into the production of IP3 and DAG, which has been shown to promote Ca2+ release from intracellular stores, activate PKC, and locally deplete PIP2 levels (Delmas and Brown, 2005).

Gene_expression (production) of IP3

19) Confidence 0.04 Published 2010 Journal Neuron Section Body Doc Link PMC3003154 Disease Relevance 0.07 Pain Relevance 0.17

proteins with subsequent phospholipase C activation, generation of inositol 1,4,5-triphosphate (IP3), and intracellular Ca2+ release.

Gene_expression (generation) of IP3

20) Confidence 0.04 Published 2008 Journal Diabetes Section Body Doc Link PMC2494688 Disease Relevance 0.14 Pain Relevance 0.15

General Comments

This test has worked.