INT110400

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Context Info
Confidence 0.50
First Reported 2003
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 21
Total Number 21
Disease Relevance 0.58
Pain Relevance 1.14

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

signal transduction (Pde1b) nucleus (Pde1b) cytoplasm (Pde1b)
Pde1b (Mus musculus)
Pain Link Frequency Relevance Heat
Glutamate receptor 21 98.80 Very High Very High Very High
agonist 22 96.24 Very High Very High Very High
antagonist 22 95.20 Very High Very High Very High
Central nervous system 38 93.52 High High
long-term potentiation 76 91.60 High High
Kinase C 19 86.72 High High
gABA 209 84.92 Quite High
interneuron 19 76.16 Quite High
Glutamate 3 75.00 Quite High
Serotonin 19 71.88 Quite High
Disease Link Frequency Relevance Heat
Pulmonary Hypertension 66 99.40 Very High Very High Very High
Disease 17 95.36 Very High Very High Very High
Apoptosis 2 75.92 Quite High
Adhesions 38 59.92 Quite High
Depression 171 47.24 Quite Low
Hypoxia 4 45.32 Quite Low
Renal Insufficiency 1 23.68 Low Low
Cirrhosis 1 10.88 Low Low
Increased Venous Pressure Under Development 5 6.36 Low Low
Cv General 4 Under Development 22 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Indeed, a reduction of PDE1 activity increased cAMP, facilitating the PKA activity and DARPP-32 phosphorylation.
Negative_regulation (reduction) of PDE1
1) Confidence 0.50 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
PDE1 inhibition did not significantly affect the [Ca2+]i increase triggered by each conditioning depolarization (Figure 7C) or the basal GABAAR responsiveness (Supplementary Table 1).
Negative_regulation (inhibition) of PDE1
2) Confidence 0.50 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.03
As summarized in Figure 8H, inhibition of PDE1, but not of PDE4 or calcineurin, significantly lowered the threshold for RP induction.
Negative_regulation (inhibition) of PDE1
3) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
Thus, the activity level of CaMKII seemed to mainly rely on the CaMKII autophosphorylation rather than PDE1 inhibition.
Negative_regulation (inhibition) of PDE1
4) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
This theoretical prediction was confirmed by electrophysiological experiments showing that inhibition of PDE1, but not that of PDE4 or calcineurin, markedly lowered the [Ca2+]i threshold for RP induction.
Negative_regulation (inhibition) of PDE1
5) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
Altogether, the kinetic simulation model for the RP regulation includes two feedforward inhibitory pathways (PDE1 and calcineurin pathways) and two positive-feedback loops (autophosphorylation of CaMKII Thr286/287 and inhibition of PDE1 by CaMKII).
Negative_regulation (inhibition) of PDE1
6) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.06
It was also reported that mutant mice lacking PDE1B show deficits in spatial learning (Reed et al, 2002).


Negative_regulation (lacking) of PDE1B
7) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0.06 Pain Relevance 0.12
Next, we analyzed how the Ca2+ thresholds calculated in the 843 cases with different parameter sets were affected by reducing the amount of PDE1, calcineurin, or PDE4 (see Supplementary information).
Negative_regulation (reducing) of PDE1
8) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.08
When PDE1 was inhibited by 8-MM-IBMX, conditioning stimulation consisting of 40-ms depolarization pulses was sufficient to induce RP (500 ms, 174±7%; 100 ms, 172±28%; 60 ms, 177±2%; 40 ms, 173±15%; 20 ms, 99±6%) (Figure 8C).
Negative_regulation (inhibited) of PDE1
9) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.06
In summary, sustained CaMKII activation and GABAAR phosphorylation were accompanied by long-term decreases in the amounts of active PP-1 and PDE1 (Figure 2E and J), and by sustained increases in the amounts of phospho-DARPP-32, cAMP, and active PKA (Figure 2A, B, and G–I).
Negative_regulation (decreases) of PDE1
10) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.03
Thus, the PDE1-mediated feedforward inhibition of CaMKII and the positive-feedback loop consisting of CaMKII-mediated PDE1 inhibition might underlie regulation of the threshold and/or the maintenance of many forms of synaptic plasticity.
Negative_regulation (inhibition) of PDE1
11) Confidence 0.37 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.09
Thus, it is likely that CaMKII-mediated inhibition of PDE1 in turn supports the CaMKII activity.
Negative_regulation (inhibition) of PDE1
12) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
The synergistic action of CaMKII autophosphorylation at Thr286/287 and PDE1 inhibition by CaMKII underlies the state switching of molecular networks regulating RP.
Negative_regulation (inhibition) of PDE1
13) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.04
Thus, CaMKII-mediated inhibition of PDE1 was incorporated into the model.
Negative_regulation (inhibition) of PDE1
14) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.14
To elucidate the role of PDE1 inhibition by CaMKII, we analyzed how the CaMKII activity affects the PP-1 activity through PDE1 phosphorylation.
Negative_regulation (inhibition) of PDE1
15) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
The effect of autophosphorylation at Thr286/287 on CaMKII activation peaked rapidly during the [Ca2+]i increase, whereas that of PDE1 inhibition became stronger about 100 s after the [Ca2+]i increase (Figure 5G; Supplementary Figure 4), when the decrease of CaMKII activity was suppressed.
Negative_regulation (inhibition) of PDE1
16) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
The reduction of PDE1 caused a leftward shift of the concentration–response curve for CaMKII activation by a transient [Ca2+]i increase (Figure 6E).
Negative_regulation (reduction) of PDE1
17) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0
This sustained decrease of PDE1 activity was caused by CaMKII-mediated reduction of the affinity of PDE1 for Ca2+/CaM, as described below.
Negative_regulation (decrease) of PDE1
18) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.06
Another PDE1 inhibitor, vinpocetine (100 ?
Negative_regulation (inhibitor) of PDE1
19) Confidence 0.36 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.03
One study comparing sildenafil to inhaled NO (iNO) demonstrated comparable reductions in PA pressures and pulmonary vascular resistance (PVR), but increased cardiac index (CI) was seen only with sildenafil treatment, consistent with an inotropic effect.24 However, other investigators, examining load-independent measures of myocardial performance, found no changes in systolic or diastolic function with sildenafil treatment.25 Circulating endothelial progenitor cells are reduced in idiopathic PAH and congenital PAH, and treatment with sildenafil has been shown to increase these cells to levels consistently higher than other PAH therapies.26 Sildenafil also inhibits PDE-1, which is expressed in low levels in the pulmonary circulation under baseline conditions but is upregulated in the disease state.27 The clinical significance of these findings remains uncertain.
Negative_regulation (inhibits) of PDE-1 associated with pulmonary hypertension and disease
20) Confidence 0.09 Published 2010 Journal Drug design, development and therapy Section Body Doc Link PMC2880338 Disease Relevance 0.52 Pain Relevance 0

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