INT257213

Context Info Confidence 0.36 First Reported 2008 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 5 Total Number 6 Disease Relevance 1.69 Pain Relevance 0.30

cytosol (PDE4A) signal transduction (PDE4A) plasma membrane (PDE4A) nucleus (PDE4A) cytoplasm (PDE4A)

Anatomy Link Frequency immune cell 1 B-cell 1 Purkinje cells 1 PDE4A (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 153 91.76 Hippocampus 8 72.48 antagonist 4 71.52 Thalamus 3 50.12 Inflammatory response 4 14.80 agonist 6 8.72 nMDA receptor 27 5.00 Inflammatory mediators 16 5.00 Central nervous system 15 5.00 Neurotransmitter 15 5.00

Disease Link Frequency Relevance Heat Shock 3 98.10 Cancer 35 95.80 Hodgkin's Disease 8 94.96 INFLAMMATION 177 91.76 Disease 24 88.68 Hypertension 20 85.56 Acromegaly 8 85.12 Pulmonary Disease 124 79.80 Reprotox - General 2 8 69.76 Obesity 8 62.44

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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 ?

PDE4 Spec (appear) Binding (appear) of in Purkinje cells

1) Confidence 0.36 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2610389 Disease Relevance 0 Pain Relevance 0.06

A few selective inhibitors of PDE7 have now been identified (Giembycz 2005) and using these it is becoming clear that inhibition of PDE7A can regulate proinflammatory and immune cell function when used in associated with PDE4 inhibitors.

PDE4 Binding (associated) of in immune cell

2) Confidence 0.19 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2650605 Disease Relevance 0.44 Pain Relevance 0.11

Siguazodan, a PDE3 inhibitor, potentiated relaxation induced by rolipram suggesting an interaction between PDE3 inhibition and PDE4 inhibition (Torphy et al 1993).

PDE4 Binding (interaction) of

3) Confidence 0.19 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2650605 Disease Relevance 0.31 Pain Relevance 0.09

PDE3 differs from PDE4 in that it has high affinity for both cAMP and cGMP so that these substrates are mutually competitive and thus PDE3 hydrolysis of cAMP can be inhibited by cGMP.

PDE4 Binding (affinity) of

4) Confidence 0.19 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2650605 Disease Relevance 0.17 Pain Relevance 0.04

PDE4 also forms another macromolecular signaling complex with ?

PDE4 Binding (complex) of

5) Confidence 0.19 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2650605 Disease Relevance 0.05 Pain Relevance 0

The R81X is a known functional mutation that codes for a truncated protein lacking the tetratricopeptide repeat (TPR) carboxy terminal domains, which are essential for AIP to bind to the aryl hydrocarbon receptor (AHR) and heat shock 90 (HSP90).12,27 Previous in vitro studies of the R81X mutation have shown that it blocks the interaction of wild type AIP and phosphodiesterase type 4A (PDE4A), potentially disrupting the cAMP cascade.28 AIP somatic status in the somatotropinoma, adrenocortical tumor and B-cell non-Hodgkin lymphoma

PDE4A Binding (interaction) of in B-cell associated with cancer, shock and hodgkin's disease

6) Confidence 0.05 Published 2010 Journal Clinics (Sao Paulo) Section Body Doc Link PMC2862671 Disease Relevance 0.71 Pain Relevance 0

General Comments

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