INT148403

Context Info Confidence 0.42 First Reported 2006 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 17 Total Number 18 Disease Relevance 7.74 Pain Relevance 2.19

signal transduction (Chrm2) plasma membrane (Chrm2) signal transducer activity (Chrm2)

Anatomy Link Frequency plasma cells 3 macrophages 2 uterine 2 ileum 1 trachea 1 Chrm2 (Mus musculus)

Pain Link Frequency Relevance Heat Dismenorea 2 99.78 Inflammation 295 99.16 antagonist 150 97.52 agonist 136 96.92 chemokine 9 93.44 cytokine 56 93.04 adenocard 7 86.32 Inflammatory mediators 16 73.88 Inflammatory response 13 68.16 Potency 112 63.56

Disease Link Frequency Relevance Heat Dysmenorrhea 2 99.78 INFLAMMATION 340 99.16 Atherosclerosis 20 98.88 Disease 30 97.92 Cancer 330 97.68 Infection 114 97.32 Targeted Disruption 454 96.48 Pulmonary Disease 51 93.88 Viral Infection 9 87.88 Occupational Lung Diseases 3 86.72

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Activation of M2 receptors alone did not cause uterine contractions; however, M2 receptor activation enhanced M3 receptor-mediated contractions in the mouse uterus.

Positive_regulation (Activation) of M2 in uterine associated with dismenorea

1) Confidence 0.42 Published 2008 Journal Naunyn Schmiedebergs Arch. Pharmacol. Section Abstract Doc Link 18071676 Disease Relevance 0.16 Pain Relevance 0.15

Activation of M2 receptors alone did not cause uterine contractions; however, M2 receptor activation enhanced M3 receptor-mediated contractions in the mouse uterus.

Positive_regulation (activation) of M2 in uterine associated with dismenorea

2) Confidence 0.42 Published 2008 Journal Naunyn Schmiedebergs Arch. Pharmacol. Section Abstract Doc Link 18071676 Disease Relevance 0.15 Pain Relevance 0.10

In trachea, M2 receptor activation opposes forskolin- but not isoproterenol-induced relaxation, which is consistent with the postulate that the ?

Positive_regulation (activation) of M2 in trachea

3) Confidence 0.31 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0 Pain Relevance 0.04

Thus, it seems likely that under some conditions M2 activation of Vav may lead to Blimp-1 expression and entry into the plasma cell program (Fig. 6E).

Positive_regulation (activation) of M2 in plasma cell

4) Confidence 0.28 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2777334 Disease Relevance 0.15 Pain Relevance 0

This explains why there is little increase in conductance unless both the M2 and the Ca2+-mobilizing M3 receptor are activated simultaneously.

Positive_regulation (activated) of M2

5) Confidence 0.27 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0 Pain Relevance 0.08

Circumstantial evidence suggests that the latter is involved in heterologous desensitization, which requires activation of both M2 and M3 receptors and is potently antagonized by M2 selective antagonists (Griffin et al. 2004).

Positive_regulation (activation) of M2 associated with antagonist

6) Confidence 0.22 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0.45 Pain Relevance 0.05

One is a highly potent M2 receptor-mediated inhibition of forskolin- and ?

Positive_regulation (potent) of M2

7) Confidence 0.22 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0.37 Pain Relevance 0.03

Studies on the mouse uterus are consistent with a conditional role for the M2 receptor in contraction (Kitazawa et al. 2008).

Positive_regulation (role) of M2 in uterus

8) Confidence 0.22 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0.24 Pain Relevance 0.03

Stimulation of the M2 receptor activates a nonselective cation conductance; however, the conductance depends on Ca2+ (Bolton 1979; Inoue 1991; Sakamoto et al. 2007).

Positive_regulation (Stimulation) of M2

9) Confidence 0.21 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0 Pain Relevance 0.06

M2 is required for differentiation of MHV68 infected B cells to plasma cells

Positive_regulation (required) of M2 in plasma cells

10) Confidence 0.20 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2777334 Disease Relevance 0.45 Pain Relevance 0

Because we have previously shown that dose of M2.Stop virus can impact the phenotype observed [18], we assessed whether increasing the dose of M2.Stop from 100 to 1,000 pfu would lead to detectable M2.Stop virus infection of plasma cells.

Spec (whether) Positive_regulation (increasing) of M2 in plasma cells associated with infection

11) Confidence 0.20 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2777334 Disease Relevance 0.34 Pain Relevance 0

The results are consistent with the postulate that 4-DAMP mustard treatment selectively inactivates M3 responses over M2, thereby converting the muscarinic behavior of the wild-type ileum into that of the M3 KO ileum.

Positive_regulation (inactivates) of M2 in ileum associated with targeted disruption

12) Confidence 0.19 Published 2009 Journal Naunyn Schmiedebergs Arch Pharmacol Section Body Doc Link PMC2749929 Disease Relevance 0.63 Pain Relevance 0

However, M2 antibodies were only stimulated when M2 was in combination with NP, suggesting possible immune synergy of the two gene products.

Positive_regulation (stimulated) of M2

13) Confidence 0.07 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2843722 Disease Relevance 0.63 Pain Relevance 0

PPARs and M2 activation of macrophages

Positive_regulation (activation) of M2 in macrophages

14) Confidence 0.05 Published 2008 Journal PPAR Research Section Body Doc Link PMC2443396 Disease Relevance 0.98 Pain Relevance 0.53

The expression of the nuclear peroxisome proliferator-activated receptors (PPARs) is regulated by M1- or M2-inducing stimuli, and these receptors are generally considered to counteract inflammatory M1 macrophages, while actively promoting M2 activation.

Positive_regulation (activation) of M2 in M1 macrophages associated with inflammation

15) Confidence 0.05 Published 2008 Journal PPAR Research Section Abstract Doc Link PMC2443396 Disease Relevance 0.82 Pain Relevance 0.25

ligands could be a valuable means of inducing M2 markers in vivo and altering macrophage functions [85].

Positive_regulation (inducing) of M2 in macrophage

16) Confidence 0.05 Published 2008 Journal PPAR Research Section Body Doc Link PMC2443396 Disease Relevance 0.53 Pain Relevance 0.30

PPARs not only antagonize M1 activation, but actually support M2 activation.

Positive_regulation (activation) of M2

17) Confidence 0.05 Published 2008 Journal PPAR Research Section Body Doc Link PMC2443396 Disease Relevance 0.90 Pain Relevance 0.48

In guinea pigs, ozone and allergen-induced M2 dysfunction is mediated by eosinophils that are recruited to airway nerves, and secrete major basic protein, that acts as an allosteric muscarinic M2 receptor antagonist [55].

Positive_regulation (induced) of M2 in nerves associated with antagonist

18) Confidence 0.03 Published 2006 Journal Respir Res Section Body Doc Link PMC1479816 Disease Relevance 0.95 Pain Relevance 0.08

General Comments

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