INT73127

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Context Info
Confidence 0.76
First Reported 1997
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 18
Total Number 21
Disease Relevance 5.25
Pain Relevance 3.31

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (Pde5a) signal transduction (Pde5a)
Anatomy Link Frequency
brain 3
cardiac myocytes 2
lung 2
skeletal muscles 1
Purkinje cells 1
Pde5a (Mus musculus)
Pain Link Frequency Relevance Heat
long-term potentiation 555 99.76 Very High Very High Very High
nMDA receptor 180 99.54 Very High Very High Very High
agonist 42 98.44 Very High Very High Very High
Delta opioid receptors 1 98.08 Very High Very High Very High
opioid receptor 4 96.48 Very High Very High Very High
tolerance 5 96.00 Very High Very High Very High
Hippocampus 129 95.88 Very High Very High Very High
Kappa opioid receptor 1 91.28 High High
Neurotransmitter 144 90.36 High High
Spinal cord 5 87.68 High High
Disease Link Frequency Relevance Heat
Increased Venous Pressure Under Development 53 99.76 Very High Very High Very High
Pulmonary Hypertension 264 99.74 Very High Very High Very High
Disease 131 98.16 Very High Very High Very High
Cognitive Disorder 852 94.88 High High
Anxiety Disorder 108 81.72 Quite High
Targeted Disruption 153 81.56 Quite High
Hypoxia 16 80.64 Quite High
Syndrome 9 68.76 Quite High
Aging 54 65.84 Quite High
Pressure Volume 2 Under Development 26 45.44 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The hypertrophied RV demonstrates increased tissue expression of PDE-5.23 In healthy individuals, PDE-5 is expressed in the coronary arteries, but is not typically found in cardiac myocytes.
Gene_expression (expressed) of PDE-5 in cardiac myocytes
1) Confidence 0.76 Published 2010 Journal Drug design, development and therapy Section Body Doc Link PMC2880338 Disease Relevance 0.54 Pain Relevance 0
The hypertrophied RV demonstrates increased tissue expression of PDE-5.23 In healthy individuals, PDE-5 is expressed in the coronary arteries, but is not typically found in cardiac myocytes.
Gene_expression (expression) of PDE-5 in cardiac myocytes
2) Confidence 0.66 Published 2010 Journal Drug design, development and therapy Section Body Doc Link PMC2880338 Disease Relevance 0.49 Pain Relevance 0
PDE-5 has been the focus for PAH because the PDE-5 enzyme is highly expressed in lung tissue compared to other vascular beds, with minimal expression in the systemic circulation.15,16 PDE-5 expression is upregulated in PAH, leading to increased metabolism of NO-derived cGMP.
Gene_expression (expressed) of PDE-5 in lung associated with pulmonary hypertension
3) Confidence 0.59 Published 2010 Journal Drug design, development and therapy Section Body Doc Link PMC2880338 Disease Relevance 0.81 Pain Relevance 0
PDE-5 has been the focus for PAH because the PDE-5 enzyme is highly expressed in lung tissue compared to other vascular beds, with minimal expression in the systemic circulation.15,16 PDE-5 expression is upregulated in PAH, leading to increased metabolism of NO-derived cGMP.
Gene_expression (expression) of PDE-5 in lung associated with pulmonary hypertension
4) Confidence 0.51 Published 2010 Journal Drug design, development and therapy Section Body Doc Link PMC2880338 Disease Relevance 0.92 Pain Relevance 0
In addition, is has been shown that expression of PDE5 is strongly reduced in brains of Alzheimer’s disease patients (Reyes-Irisarri et al. 2007).
Gene_expression (expression) of PDE5 in brains associated with disease
5) Confidence 0.34 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0.53 Pain Relevance 0.13
PDE5 has been detected in the brain, lungs, smooth and skeletal muscles, kidneys, and platelets (Giordano et al. 2001; Hotston et al. 2007; Kotera et al. 2000; Yanaka et al. 1998).
Gene_expression (detected) of PDE5 in skeletal muscles
6) Confidence 0.34 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0 Pain Relevance 0
The latter can activate GC, which produces the second messenger cGMP.
Gene_expression (produces) of cGMP
7) Confidence 0.30 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0 Pain Relevance 0.28
However, zaprinast is not selective for PDE5, as it also inhibits PDE1, 9, 10, and 11 (Bender and Beavo 2006).
Neg (not) Gene_expression (selective) of PDE5
8) Confidence 0.30 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 1.21 Pain Relevance 0.03
As presynaptic cGMP plays a role in E-LTP, theoretically, inhibition of cGMP degradation with, for instance, a PDE9-I should, therefore, be able to influence L-LTP/LTM via E-LTP/STM as well.
Gene_expression (presynaptic) of cGMP associated with long-term potentiation
9) Confidence 0.26 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0 Pain Relevance 0.35
Presynaptic cGMP is involved in E-LTP (LTP1) (Arancio et al. 1995), but cAMP is probably not (Nguyen and Woo 2003).
Gene_expression (Presynaptic) of cGMP associated with long-term potentiation
10) Confidence 0.26 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0.07 Pain Relevance 0.24
Presynaptic cGMP is involved in E-LTP (LTP1) (Arancio et al. 1995), but cAMP is probably not (Nguyen and Woo 2003).
Gene_expression (involved) of cGMP associated with long-term potentiation
11) Confidence 0.26 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0.07 Pain Relevance 0.24
It emerged as a signalling molecule in the brain 20 years ago following the search for a missing transmitter that was generated in response to neuronal NMDA receptor activation and caused cGMP generation in other cells (Table 1).
Gene_expression (generation) of cGMP in brain associated with nmda receptor
12) Confidence 0.24 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.16
For example, cerebellar Purkinje cells all appear to contain PDE5 but a subset additionally expresses a PDE1 isoform (Shimizu-Albergine et al., 2003); in cerebellar astrocytes PDE5 is also prominent but PDE4, which has low affinity (> 100 ?
Gene_expression (contain) of PDE5 in Purkinje cells
13) Confidence 0.24 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.03
This is because PDE-Is increase the levels of cAMP and cGMP, and vasodilatation properties can be attributed to both cyclic nucleotides (Dundore et al. 1993; Paterno et al. 1996).
Gene_expression (levels) of cGMP associated with increased venous pressure under development
14) Confidence 0.23 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0.61 Pain Relevance 0.04
Recently, the cyclic guanosine monophosphate (cGMP) second messenger system receives more and more attention. cGMP is produced by guanylate cyclase (GC) which is stimulated by nitric oxide (NO) (Murad et al. 1978). cGMP activates cGMP-dependent protein kinase (PKG), which in turn phosphorylates certain proteins which influence the synthesis and/or release of other neurotransmitters, and thus signal transduction (Schmidt et al. 1993).
Gene_expression (produced) of cGMP associated with neurotransmitter
15) Confidence 0.23 Published 2008 Journal Psychopharmacology (Berl) Section Body Doc Link PMC2704616 Disease Relevance 0 Pain Relevance 0.05
Transduction of cGMP signals
Gene_expression (signals) of cGMP
16) Confidence 0.21 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.08
m) for cGMP (?
Gene_expression (for) of cGMP
17) Confidence 0.21 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.04
Hydrolysis of cGMP
Gene_expression (Hydrolysis) of cGMP
18) Confidence 0.21 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.06
Whilst traditionally acting intracellularly, cGMP is also found extracellularly in the brain, where its levels fluctuate according to changes in endogenous NO formation (reviewed by Vincent et al., 1998; Pepicelli et al., 2004). cGMP can be exported from cells through members of the multidrug resistance protein family (reviewed by Sager, 2004) and might serve an additional intercellular signalling role, consistent with evidence that extracellularly applied cGMP has biological effects (Touyz et al., 1997; Poulopoulou & Nowak, 1998; Montoliu et al., 1999).


Gene_expression (exported) of cGMP in brain
19) Confidence 0.21 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.08
Since activation of NO increases the production of cGMP, the present results demonstrating alterations of cGMP levels by mu-, kappa- and delta-opioid receptor agonists are consistent with the behavioral results with NOS inhibitors on tolerance to mu-, kappa- and delta-opioid receptor agonists.
Gene_expression (production) of cGMP associated with tolerance, agonist and opioid receptor
20) Confidence 0.09 Published 1997 Journal Peptides Section Abstract Doc Link 9437726 Disease Relevance 0 Pain Relevance 1.21

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