INT109110

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Context Info
Confidence 0.63
First Reported 2003
Last Reported 2010
Negated 1
Speculated 2
Reported most in Body
Documents 29
Total Number 33
Disease Relevance 11.16
Pain Relevance 16.65

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
smooth muscle 2
nucleus 2
liver 1
spinal cord 1
brain 1
Pde5a (Rattus norvegicus)
Pain Link Frequency Relevance Heat
amygdala 294 100.00 Very High Very High Very High
Bioavailability 4 100.00 Very High Very High Very High
pregabalin 104 99.92 Very High Very High Very High
analgesia 6 99.90 Very High Very High Very High
spinal dorsal horn 4 99.88 Very High Very High Very High
antinociception 127 99.54 Very High Very High Very High
gABA 77 99.44 Very High Very High Very High
Opioid 15 99.06 Very High Very High Very High
opioid receptor 49 98.80 Very High Very High Very High
Hyperalgesia 74 98.62 Very High Very High Very High
Disease Link Frequency Relevance Heat
Hypotension 22 99.78 Very High Very High Very High
Hyperalgesia 84 98.62 Very High Very High Very High
Hypoactive Sexual Desire Disorder 13 98.60 Very High Very High Very High
INFLAMMATION 51 98.58 Very High Very High Very High
Cirrhosis 5 97.84 Very High Very High Very High
Anxiety Disorder 166 97.76 Very High Very High Very High
Increased Venous Pressure Under Development 65 97.72 Very High Very High Very High
Pain 123 97.68 Very High Very High Very High
Nociception 56 97.40 Very High Very High Very High
Immunotherapy Of Cancer 32 97.24 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Previous studies demonstrated increased phosphodiesterase-5 (PDE5) activity and expression in the kidneys of rats with liver cirrhosis.
Positive_regulation (increased) of PDE5 in liver associated with cirrhosis
1) Confidence 0.63 Published 2007 Journal Eur. J. Pharmacol. Section Abstract Doc Link 17610866 Disease Relevance 0.31 Pain Relevance 0.04
While the mechanism of interaction is unknown, it is hypothesized that sildenafil may exhibit a PD synergistic interaction with pregabalin by increasing intracellular concentrations of cGMP.
Positive_regulation (increasing) of cGMP associated with pregabalin
2) Confidence 0.42 Published 2009 Journal Pharm Res Section Body Doc Link PMC2737110 Disease Relevance 0.59 Pain Relevance 0.79
In turn, increased intracellular cGMP may amplify downstream regulation of the VGCC and modify pain perception in neuropathic pain.
Positive_regulation (increased) of cGMP associated with pain, calcium channel and neuropathic pain
3) Confidence 0.42 Published 2009 Journal Pharm Res Section Body Doc Link PMC2737110 Disease Relevance 0.59 Pain Relevance 0.79
The progression of endothelium dysfunction and of penile vascular disease, androgen deficiency, reduced sexual desire and appealing, and psychogenic issues are often the reason for a low response to PDE-5 inhibition (McMahon 2004).
Positive_regulation (response) of PDE-5 in endothelium associated with hypoactive sexual desire disorder and increased venous pressure under development
4) Confidence 0.37 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.43 Pain Relevance 0
In these patients, either psychogenic erections or reflexive spinally elicited erections or both are necessary for PDE5 inhibitor response.
Positive_regulation (necessary) of PDE5
5) Confidence 0.37 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0.22 Pain Relevance 0.05
Chronic PDE inhibition, via the persistent activation of PDE5 promoters, may up-regulate PDE expression and, therefore, be associated with the development of drug tachyphylaxis (Moreland et al 1999).
Positive_regulation (activation) of PDE5
6) Confidence 0.34 Published 2006 Journal Clinical Interventions in Aging Section Body Doc Link PMC2699638 Disease Relevance 0 Pain Relevance 0
However, it has not been known what increased cGMP by sildenafil could exert on opioid receptor, further research including receptor binding study will be necessary.
Positive_regulation (increased) of cGMP associated with opioid receptor
7) Confidence 0.29 Published 2008 Journal Journal of Korean Medical Science Section Body Doc Link PMC2610640 Disease Relevance 0.47 Pain Relevance 0.87
The increased concentration of cGMP activates protein kinase G, also called cGMP-dependent kinase, which through phosphorylation of ion channels opens potassium channels and inhibits calcium channels.
Positive_regulation (activates) of cGMP associated with calcium channel and potassium channel
8) Confidence 0.26 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643112 Disease Relevance 0.07 Pain Relevance 0.21
There are increasing experimental data that increased concentrations of NO and cGMP have an antifibrotic effect on tissues including the tunica albuginea and corporal tissue, supporting a role for tadalafil to halt the pathophysiologic role of CVOD in post-prostate cancer treatment ED.
Positive_regulation (increased) of cGMP in tunica albuginea associated with erectile dysfunction and immunotherapy of cancer
9) Confidence 0.23 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643112 Disease Relevance 1.25 Pain Relevance 0.16
These observations may be a result of increased cGMP causing a decrease in prostatic muscle tension (Uckert et al 2001), NO effect on the smooth muscle of the bladder, PDE inhibition in the prostate and prostatic urethra, or some other process not yet defined.
Positive_regulation (increased) of cGMP in prostatic urethra associated with stress incontinence
10) Confidence 0.23 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643112 Disease Relevance 0.65 Pain Relevance 0
By inhibiting the breakdown of cGMP, PDE5 inhibitors create increased bioavailability of cGMP, which both facilitates and potentiates the NO-mediated relaxation of erectile smooth muscle with sexual stimulation.
Positive_regulation (increased) of cGMP in smooth muscle associated with bioavailability
11) Confidence 0.21 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2643112 Disease Relevance 0.20 Pain Relevance 0.09
These findings suggest that inhibition of this enzyme, in turn, may increase the level of cGMP, thereby producing antinociception.
Spec (may) Positive_regulation (increase) of cGMP associated with antinociception
12) Confidence 0.21 Published 2008 Journal Journal of Korean Medical Science Section Body Doc Link PMC2610640 Disease Relevance 0.58 Pain Relevance 1.15
Therefore, it is conceivable that the increased cGMP level by inhibition of phosphodiesterase may contribute to the antinociception in the spinal cord.
Positive_regulation (increased) of cGMP in spinal cord associated with antinociception and spinal cord
13) Confidence 0.21 Published 2008 Journal Journal of Korean Medical Science Section Body Doc Link PMC2610640 Disease Relevance 0.58 Pain Relevance 0.70
Furthermore, several lines of evidence suggest that opioid-induced antinociception may be related to the activation of the NO-cGMP pathway (15-17).
Positive_regulation (activation) of cGMP associated with antinociception and opioid
14) Confidence 0.20 Published 2008 Journal Journal of Korean Medical Science Section Body Doc Link PMC2610640 Disease Relevance 0.97 Pain Relevance 1.16
Oral sildenafil moderately reduced blood pressure in normal humans.35 Furthermore, a significant decrease of blood pressure was transiently observed with intravenous sildenafil in healthy men, whereas HR was not affected.36 Particularly, the combination of sildenafil with nitric oxide donors can potentiate the hypotensive effect by accumulation of cGMP.37 Therefore, the concomitant use of sildenafil with any drug which serves as a nitric oxide donor is absolutely contraindicated in clinics.38
Positive_regulation (accumulation) of cGMP in blood associated with pressure volume 2 under development and hypotension
15) Confidence 0.16 Published 2010 Journal Yonsei Medical Journal Section Body Doc Link PMC2799976 Disease Relevance 0.34 Pain Relevance 0.42
It would therefore, appear that cGMP analog increases the synaptic GABA release to labeled paraventricular nucleus neurons.32,33 And increasing cGMP level by superfusing slices with another phosphodiesterase inhibitor (zaprinast) increases GABA release in the brain stem, while a guanylyl cyclase inhibitor (ODQ) reduces GABA release.15 Recently, it has been demonstrated that potassium channels are downstream effectors of cGMP on GABA release.33 Furthermore, the antinociception provoked by sildenafil and dibutyryl-cGMP was reversed by potassium channel blockers.10,34 These findings together suggest that intravenous sildenafil increases the cGMP level by inhibition of phosphodiesterase 5 and then induces the release of GABA through a downstream mechanism, involving potassium channels which act on GABA receptors, in turn leading to an antinociceptive effect.
Positive_regulation (increasing) of cGMP in nucleus associated with antinociception, gaba, gaba receptor, potassium channel and antinociceptive
16) Confidence 0.16 Published 2010 Journal Yonsei Medical Journal Section Body Doc Link PMC2799976 Disease Relevance 0 Pain Relevance 1.00
Elevation of intracellular cAMP levels suppresses the activity of immune and inflammatory cells (Bourne et al 1974; Kammer 1988; Moore and Willoughby 1995) and elevation of both cAMP and cGMP leads to smooth muscle relaxation. cAMP may have an additional role in modulating airway smooth muscle hypertrophy and hyperplasia as it has cytostatic effects in many cell types (Pastan et al 1975; Friedman et al 1976), and exerts an inhibitory effect influence on airway smooth muscle proliferation (Lew et al 1992; Tomlinson et al 1995).
Positive_regulation (elevation) of cGMP in smooth muscle associated with hypertrophy, inflammation and hyperplasia
17) Confidence 0.12 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2650605 Disease Relevance 0.38 Pain Relevance 0.08
It would therefore, appear that cGMP analog increases the synaptic GABA release to labeled paraventricular nucleus neurons.32,33 And increasing cGMP level by superfusing slices with another phosphodiesterase inhibitor (zaprinast) increases GABA release in the brain stem, while a guanylyl cyclase inhibitor (ODQ) reduces GABA release.15 Recently, it has been demonstrated that potassium channels are downstream effectors of cGMP on GABA release.33 Furthermore, the antinociception provoked by sildenafil and dibutyryl-cGMP was reversed by potassium channel blockers.10,34 These findings together suggest that intravenous sildenafil increases the cGMP level by inhibition of phosphodiesterase 5 and then induces the release of GABA through a downstream mechanism, involving potassium channels which act on GABA receptors, in turn leading to an antinociceptive effect.
Positive_regulation (increases) of cGMP in neurons associated with antinociception, gaba, gaba receptor, potassium channel and antinociceptive
18) Confidence 0.12 Published 2010 Journal Yonsei Medical Journal Section Body Doc Link PMC2799976 Disease Relevance 0.07 Pain Relevance 0.82
Guanylyl cyclase catalyzes the formation of cyclic guanosine monophosphate (cGMP) from GTP, leading to the synthesis of cGMP, whereas cGMP-specific phosphodiesterase catalyzes the hydrolysis of cGMP to GMP.2 Accordingly, intracellular cGMP concentrations are regulated by the action of guanylyl cyclase and the rate of degradation by cGMP-specific phosphodiesterase.6,7
Positive_regulation (concentrations) of cGMP
19) Confidence 0.12 Published 2010 Journal Yonsei Medical Journal Section Body Doc Link PMC2799976 Disease Relevance 1.11 Pain Relevance 1.40
It would therefore, appear that cGMP analog increases the synaptic GABA release to labeled paraventricular nucleus neurons.32,33 And increasing cGMP level by superfusing slices with another phosphodiesterase inhibitor (zaprinast) increases GABA release in the brain stem, while a guanylyl cyclase inhibitor (ODQ) reduces GABA release.15 Recently, it has been demonstrated that potassium channels are downstream effectors of cGMP on GABA release.33 Furthermore, the antinociception provoked by sildenafil and dibutyryl-cGMP was reversed by potassium channel blockers.10,34 These findings together suggest that intravenous sildenafil increases the cGMP level by inhibition of phosphodiesterase 5 and then induces the release of GABA through a downstream mechanism, involving potassium channels which act on GABA receptors, in turn leading to an antinociceptive effect.
Spec (appear) Positive_regulation (increases) of cGMP in nucleus associated with antinociception, gaba, gaba receptor, potassium channel and antinociceptive
20) Confidence 0.12 Published 2010 Journal Yonsei Medical Journal Section Body Doc Link PMC2799976 Disease Relevance 0 Pain Relevance 1.01

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