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Academic literature on the topic 'PDE4 inhibitor'

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Published: 11 March 2023

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Journal articles on the topic "PDE4 inhibitor"

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ERDOGAN, Suat, and Miles D. HOUSLAY. "Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a novel PDE4A splice variant." Biochemical Journal 321, no. 1 (January 1, 1997): 165–75. http://dx.doi.org/10.1042/bj3210165.

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The cAMP phosphodiesterase (PDE) 3 and PDE4 isoforms provide the major cAMP-hydrolysing PDE activities in Jurkat T-cells, with additional contributions from the PDE1 and PDE2 isoforms. Challenge of cells with the adenylate cyclase activator forskolin led to a rapid, albeit transient, increase in PDE3 activity occurring over the first 45 min, followed by a sustained increase in PDE3 activity which began after ∼3 h and continued for at least 24 h. Only this second phase of increase in PDE3 activity was blocked by the transcriptional inhibitor actinomycin D. After ∼3 h of exposure to forskolin, PDE4 activity had increased, via a process that could be inhibited by actinomycin D, and it remained elevated for at least a 24 h period. Such actions of forskolin were mimicked by cholera toxin and 8-bromo-cAMP. Forskolin increased intracellular cAMP concentrations in a time-dependent fashion and its action was enhanced when PDE induction was blocked with actinomycin D. Reverse transcription (RT)-PCR analysis, using generic primers designed to detect transcripts representing enzymically active products of the four PDE4 genes, identified transcripts for PDE4A and PDE4D but not for PDE4B or PDE4C in untreated Jurkat T-cells. Forskolin treatment did not induce transcripts for either PDE4B or PDE4C; however, it reduced the RT-PCR signal for PDE4A transcripts and markedly enhanced that for PDE4D transcripts. Using RT-PCR primers for PDE4 splice variants, a weak signal for PDE4D1 was evident in control cells whereas, in forskolin-treated cells, clear signals for both PDE4D1 and PDE4D2 were detected. RT-PCR analysis of the PDE4A species indicated that it was not the PDE4A isoform PDE-46 (PDE4A4B). Immunoblotting of control cells for PDE4 forms identified a single PDE4A species of ∼118 kDa, which migrated distinctly from the PDE4A4B isoform PDE-46, with immunoprecipitation analyses showing that it provided all of the PDE4 activity in control cells. Forskolin treatment led to a marked decrease of this novel PDE4A species and allowed the detection of a strong signal for an ∼67 kDa PDE4D species, suggested to be PDE4D1, but did not induce PDE4B and PDE4C isoforms. Elevation of intracellular cAMP concentrations in Jurkat T-cells thus exerts a highly selective effect on the transcriptional activity of the genes encoding the various PDE4 isoforms. This leads to the down-regulation of a novel PDE4A splice variant and the induction of PDE4D1 and PDE4D2 splice variants, leading to a net increase in the total PDE4 activity of Jurkat T-cells.
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Wang, Huanchen, Ming-Sheng Peng, Yi Chen, Jie Geng, Howard Robinson, Miles D. Houslay, Jiwen Cai, and Hengming Ke. "Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors." Biochemical Journal 408, no. 2 (November 14, 2007): 193–201. http://dx.doi.org/10.1042/bj20070970.

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PDE4 (phosphodiesterase-4)-selective inhibitors have attracted much attention as potential therapeutics for the treatment of both depression and major inflammatory diseases, but their practical application has been compromised by side effects. A possible cause for the side effects is that current PDE4-selective inhibitors similarly inhibit isoforms from all four PDE4 subfamilies. The development of PDE4 subfamily-selective inhibitors has been hampered by a lack of structural information. In the present study, we rectify this by providing the crystal structures of the catalytic domains of PDE4A, PDE4B and PDE4D in complex with the PDE4 inhibitor NVP {4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid} as well as the unliganded PDE4C structure. NVP binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. However, detailed structural comparison reveals significant conformational differences. Although the active sites of PDE4B and PDE4D are mostly comparable, PDE4A shows significant displacements of the residues next to the invariant glutamine residue that is critical for substrate and inhibitor binding. PDE4C appears to be more distal from other PDE4 subfamilies, with certain key residues being disordered. Our analyses provide the first structural basis for the development of PDE4 subfamily-selective inhibitors.
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Boyd, Abigail, Ileana V. Aragon, Lina Abou Saleh, Dylan Southers, and Wito Richter. "The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice." Biochemical Journal 478, no. 10 (May 24, 2021): 1891–906. http://dx.doi.org/10.1042/bcj20210212.

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Saliva, while often taken for granted, is indispensable for oral health and overall well-being, as inferred from the significant impairments suffered by patients with salivary gland dysfunction. Here, we show that treatment with several structurally distinct PAN-PDE4 inhibitors, but not a PDE3 inhibitor, induces saliva secretion in mice, indicating it is a class-effect of PDE4 inhibitors. In anesthetized mice, while neuronal regulations are suppressed, PDE4 inhibition potentiates a β-adrenoceptor-induced salivation, that is ablated by the β-blocker Propranolol and is absent from homozygous ΔF508-CFTR mice lacking functional CFTR. These data suggest that PDE4 acts within salivary glands to gate saliva secretion that is contingent upon the cAMP/PKA-dependent activation of CFTR. Indeed, PDE4 contributes the majority of total cAMP-hydrolytic capacity in submandibular-, sublingual-, and parotid glands, the three major salivary glands of the mouse. In awake mice, PDE4 inhibitor-induced salivation is reduced by CFTR deficiency or β-blockers, but also by the muscarinic blocker Atropine, suggesting an additional, central/neuronal mechanism of PDE4 inhibitor action. The PDE4 family comprises four subtypes, PDE4A-D. Ablation of PDE4D, but not PDE4A-C, produced a minor effect on saliva secretion, implying that while PDE4D may play a predominant role, PDE4 inhibitor-induced salivation results from the concurrent inactivation of multiple (at least two) PDE4 subtypes. Taken together, our data reveal a critical role for PDE4/PDE4D in controlling CFTR function in an in vivo model and in inducing salivation, hinting at a therapeutic potential of PDE4 inhibition for cystic fibrosis and conditions associated with xerostomia.
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Xu, Man, Xiaowen Yu, Xia Meng, Songming Huang, Yue Zhang, Aihua Zhang, and Zhanjun Jia. "Inhibition of PDE4/PDE4B improves renal function and ameliorates inflammation in cisplatin-induced acute kidney injury." American Journal of Physiology-Renal Physiology 318, no. 3 (March 1, 2020): F576—F588. http://dx.doi.org/10.1152/ajprenal.00477.2019.

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Nephrotoxicity is a known clinical complication of cisplatin that limits the use of this potent antitumor drug. Cyclic nucleotide phosphodiesterases (PDEs) play complex roles in physiology and pathology. PDE4, which is a member of the PDE family, has four subtypes (PDE4A–PDE4D), and PDE4B plays an important role in inflammation. Thus, in the present study, we investigated the effect of PDE4/PDE4B inhibition on renal function and inflammation in a cisplatin nephrotoxicity model. In mice, cisplatin enhanced mRNA and protein expression of PDE4B in renal tubules. After treatment with the PDE4 inhibitor cilomilast, cisplatin-induced renal dysfunction, renal tubular injury, tubular cell apoptosis, and inflammation were all improved. Next, after silencing PDE4B in vivo, we observed a protective effect against cisplatin nephrotoxicity similar to that of the PDE4 inhibitor. In vitro, cisplatin-induced renal tubular cell death was strikingly ameliorated by the PDE4 inhibitor and PDE4B knockdown along with the blockade of the inflammatory response. Considering the known roles of some cell survival pathways in antagonizing insults, we examined levels of PDE4-associated proteins sirtuin 1, phosphatidylinositol 3-kinase, and phosphorylated AKT in cisplatin-treated renal tubular cells with or without cilomilast treatment. Strikingly, cisplatin treatment downregulated the expression of the above proteins, and this effect was largely abolished by the PDE4 inhibitor. Together, these findings indicate the beneficial role of PDE4/PDE4B inhibition in treating cisplatin nephrotoxicity, possibly through antagonizing inflammation and restoring cell survival signaling pathways.
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Abusnina, Abdurazzag, Thérèse Keravis, Qingwei Zhou, Hélène Justiniano, Annelise Lobstein, and Claire Lugnier. "Tumour growth inhibition and anti-angiogenic effects using curcumin correspond to combined PDE2 and PDE4 inhibition." Thrombosis and Haemostasis 113, no. 02 (March 2015): 319–28. http://dx.doi.org/10.1160/th14-05-0454.

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SummaryVascular endothelial growth factor (VEGF) plays a major role in angiogenesis by stimulating endothelial cells. Increase in cyclic AMP (cAMP) level inhibits VEGF-induced endothelial cell proliferation and migration. Cyclic nucleotide phosphodiesterases (PDEs), which specifically hydrolyse cyclic nucleotides, are critical in the regulation of this signal transduction. We have previously reported that PDE2 and PDE4 up-regulations in human umbilical vein endothelial cells (HUVECs) are implicated in VEGF-induced angiogenesis and that inhibition of PDE2 and PDE4 activities prevents the development of the in vitro angiogenesis by increasing cAMP level, as well as the in vivo chicken embryo angiogenesis. We have also shown that polyphenols are able to inhibit PDEs. The curcumin having anti-cancer properties, the present study investigated whether PDE2 and PDE4 inhibitors and curcumin could have similar in vivo anti-tumour properties and whether the anti-angiogenic effects of curcumin are mediated by PDEs. Both PDE2/PDE4 inhibitor association and curcumin significantly inhibited in vivo tumour growth in C57BL/6N mice. In vitro, curcumin inhibited basal and VEGF-stimulated HUVEC proliferation and migration and delayed cell cycle progression at G0/G1, similarly to the combination of selective PDE2 and PDE4 inhibitors. cAMP levels in HUVECs were significantly increased by curcumin, similarly to rolipram (PDE4 inhibitor) and BAY-60–550 (PDE2 inhibitor) association, indicating cAMP-PDE inhibitions. Moreover, curcumin was able to inhibit VEGF-induced cAMP-PDE activity without acting on cGMP-PDE activity and to modulate PDE2 and PDE4 expressions in HUVECs. The present results suggest that curcumin exerts its in vitro anti-angiogenic and in vivo antitumour properties through combined PDE2 and PDE4 inhibition.
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Favot, Laure, Thérèse Keravis, Vincent Holl, Alain Bec, and Claire Lugnier. "VEGF-induced HUVEC migration and proliferation are decreased by PDE2 and PDE4 inhibitors." Thrombosis and Haemostasis 90, no. 08 (2003): 334–43. http://dx.doi.org/10.1160/th03-02-0084.

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SummaryMigration and proliferation of endothelial cells in response to VEGF play an important role in angiogenesis associated to pathologies such as atherosclerosis, diabetes and tumor development. Elevation of cAMP in endothelial cells has been shown to inhibit growth factor-induced proliferation. Our hypothesis was that inactivation of cAMP-specific phosphodiesterases (PDEs) would inhibit angiogenesis. The purpose of this study was to evaluate the effect of PDE inhibitors on in vitro and in vivo angiogenesis, using human umbilical vein endothelial cell (HUVEC) and chick chorioallantoic membrane (CAM) models respectively. Here, we report that: 1) PDE2, PDE3, PDE4 and PDE5 are expressed in HUVEC; 2) EHNA (20 µM), PDE2 selective inhibitor, and RP73401 (10 µM), PDE4 selective inhibitor, are able to increase the intracellular cAMP level in HUVEC; 3) EHNA and RP73401 are able to inhibit proliferation, cell cycle progression and migration of HUVEC stimulated by VEGF; 4) these in vitro effects can be mimic by treating HUVEC with the cAMP analogue, 8-Br-cAMP (600 µM); 5) only the association of EHNA and RP73401 inhibits in vivo angiogenesis, indicating that both migration and proliferation must be inhibited. These data strongly suggest that PDE2 and PDE4 represent new potential therapeutic targets in pathological angiogenesis.
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Ivey, F. Douglas, Lili Wang, Didem Demirbas, Christina Allain, and Charles S. Hoffman. "Development of a Fission Yeast-Based High-Throughput Screen to Identify Chemical Regulators of cAMP Phosphodiesterases." Journal of Biomolecular Screening 13, no. 1 (November 26, 2007): 62–71. http://dx.doi.org/10.1177/1087057107312127.

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Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of enzymes that serve as drug targets in many human diseases. There is a continuing need to identify high-specificity inhibitors that affect individual PDE families or even subtypes within a single family. The authors describe a fission yeast-based high-throughput screen to detect inhibitors of heterologously expressed adenosine 3′,5′-cyclic monophosphate (cAMP) PDEs. The utility of this system is demonstrated by the construction and characterization of strains that express mammalian PDE2A, PDE4A, PDE4B, and PDE8A and respond appropriately to known PDE2A and PDE4 inhibitors. High-throughput screens of 2 bioactive compound libraries for PDE inhibitors using strains expressing PDE2A, PDE4A, PDE4B, and the yeast PDE Cgs2 identified known PDE inhibitors and members of compound classes associated with PDE inhibition. The authors verified that the furanocoumarin imperatorin is a PDE4 inhibitor based on its ability to produce a PDE4-specific elevation of cAMP levels. This platform can be used to identify PDE activators, as well as genes encoding PDE regulators, which could serve as targets for future drug screens. ( Journal of Biomolecular Screening 2008:62-71)
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Yougbare, Issaka, Caroline Morin, Farid Yannick Senouvo, Chantal Sirois, Roula Albadine, Claire Lugnier, and Eric Rousseau. "NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues." American Journal of Physiology-Lung Cellular and Molecular Physiology 301, no. 4 (October 2011): L441—L450. http://dx.doi.org/10.1152/ajplung.00407.2010.

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Chronic inflammation is a hallmark of pulmonary diseases, which leads to lung parenchyma destruction (emphysema) and obstructive bronchiolitis occurring in both chronic obstructive pulmonary disease and asthma. Inflammation is strongly correlated with low intracellular cAMP levels and increase in specific cAMP hydrolyzing activity. The aim of the present study was to investigate the role of the cyclic phosphodiesterase type 4 (PDE4) in human lung and to determine the effects of NCS 613, a new PDE4 inhibitor, on lung inflammation and bronchial hyperresponsiveness. High cAMP-PDE activities were found in the cytosoluble fractions from human lung parenchyma and distal bronchi. PDE4 (rolipram sensitive) represented 40% and 56% of total cAMP-PDE activities in the above-corresponding tissues. Moreover, PDE4A, PDE4B, PDE4C, and PDE4D isoforms were detected in all three subcellular fractions (cytosolic, microsomal, and nuclear) with differential distributions according to specific variants. Pharmacological treatments with NCS 613 significantly decreased PDE4 activity and reduced IκBα degradation in cultured parenchyma, both of which are usually correlated with a lower inflammation status. Moreover, NCS 613 pretreatment potentiated isoproterenol-induced relaxations in human distal bronchi, while reducing TNF-α-induced hyperresponsiveness in cultured bronchi, as assessed in the presence of methacholine, U-46619, or histamine. This reducing effect of NCS 613 on human bronchi hyperresponsiveness triggered by TNF-α was related to a lower expression level of PDE4B and PDE4C, as well as a downregulation of the phosphorylated forms of p38-MAPK, CPI-17, and MYPT-1, which are known to control tone. In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway overreactivity.
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Boyd, Abigail, Ileana Aragon, Justin Rich, Will McDonough, Marianna Oditt, Daniel Irelan, Edward Fiedler, Lina Abou Saleh, and Wito Richter. "Assessment of PDE4 Inhibitor-Induced Hypothermia as a Correlate of Nausea in Mice." Biology 10, no. 12 (December 20, 2021): 1355. http://dx.doi.org/10.3390/biology10121355.

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Treatment with PAN-PDE4 inhibitors has been shown to produce hypothermia in multiple species. Given the growing body of evidence that links nausea and emesis to disturbances in thermoregulation in mammals, we explored PDE4 inhibitor-induced hypothermia as a novel correlate of nausea in mice. Using knockout mice for each of the four PDE4 subtypes, we show that selective inactivation of individual PDE4 subtypes per se does not produce hypothermia, which must instead require the concurrent inactivation of multiple (at least two) PDE4 subtypes. These findings contrast with the role of PDE4s in shortening the duration of α2-adrenoceptor-dependent anesthesia, a behavioral surrogate previously used to assess the emetic potential of PDE4 inhibitors, which is exclusively affected by inactivation of PDE4D. These different outcomes are rooted in the distinct molecular mechanisms that drive these two paradigms; acting as a physiologic α2-adrenoceptor antagonist produces the effect of PDE4/PDE4D inactivation on the duration of α2-adrenoceptor-dependent anesthesia, but does not mediate the effect of PDE4 inhibitors on body temperature in mice. Taken together, our findings suggest that selective inhibition of any individual PDE4 subtype, including inhibition of PDE4D, may be free of nausea and emesis.
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Murthy, Karnam S., Huiping Zhou, and Gabriel M. Makhlouf. "PKA-dependent activation of PDE3A and PDE4 and inhibition of adenylyl cyclase V/VI in smooth muscle." American Journal of Physiology-Cell Physiology 282, no. 3 (March 1, 2002): C508—C517. http://dx.doi.org/10.1152/ajpcell.00373.2001.

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Regulation of adenylyl cyclase type V/VI and cAMP-specific, cGMP-inhibited phosphodiesterase (PDE) 3 and cAMP-specific PDE4 by cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) was examined in gastric smooth muscle cells. Expression of PDE3A but not PDE3B was demonstrated by RT-PCR and Western blot. Basal PDE3 and PDE4 activities were present in a ratio of 2:1. Forskolin, isoproterenol, and the PKA activator 5,6-dichloro-1-β-d-ribofuranosyl benzimidazole 3′,5′-cyclic monophosphate, SP-isomer, stimulated PDE3A phosphorylation and both PDE3A and PDE4 activities. Phosphorylation of PDE3A and activation of PDE3A and PDE4 were blocked by the PKA inhibitors [protein kinase inhibitor (PKI) and H-89] but not by the PKG inhibitor (KT-5823). Sodium nitroprusside inhibited PDE3 activity and augmented forskolin- and isoproterenol-stimulated cAMP levels; PDE3 inhibition was reversed by blockade of cGMP synthesis. Forskolin stimulated adenylyl cyclase phosphorylation and activity; PKI blocked phosphorylation and enhanced activity. Stimulation of cAMP and inhibition of inositol 1,4,5-trisphosphate-induced Ca2+release and muscle contraction by isoproterenol were augmented additively by PDE3 and PDE4 inhibitors. The results indicate that PKA regulates cAMP levels in smooth muscle via stimulatory phosphorylation of PDE3A and PDE4 and inhibitory phosphorylation of adenylyl cyclase type V/VI. Concurrent generation of cGMP inhibits PDE3 activity and augments cAMP levels.
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Dissertations / Theses on the topic "PDE4 inhibitor"

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Reid, Anne Marie. "Raf-1 kinase inhibitor protein modulation of the cellular response to chemotherapeutic drugs and PDE5 inhibitors." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2497/.

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RKIP was initially discovered as an endogenous inhibitor of the ERK and NF-κB pathways,and was also shown to prolong the activation of GPCRs via inhibition of the GRK2 protein. Now increasing evidence has linked RKIP to a metastases suppressing and chemo-sensitising role in cancer cells.The chemo-sensitising effect of RKIP was investigated in a colon carcinoma cell line using a variety of chemotherapeutic agents from conventional agents to newer targeted therapies. Initial results suggested that role of RKIP in the modulation of chemotherapeutic drug response was at the level of apoptosis; there did not appear to be great observable effects in the cell proliferative response and the cell cycle distribution of the colon carcinoma cells after treatment with selected agents. Apoptosis modulation by RKIP occurred after treatment with doxorubicin, FasL, paclitaxel and TRAIL. TRAIL-treated colon carcinoma cells displayed increased cell death as the levels of RKIP within the cell were increased. In contrast, doxorubicin, FasL and paclitaxel-treated cells displayed a scaffold-like response as the levels of RKIP were increased in the cell; with WT RKIP-expressing cells being more sensitive to doxorubicin, FasL and paclitaxel-induced apoptosis than low or high RKIP-expressing colon carcinoma cells. There was no modulation of 5-FU, cisplatin and etoposide-induced apoptosis by RKIP. Indeed, these three agents did not appear to induce cell death in this colon carcinoma cell line. RKIP modulation of chemo-sensitivity has never been shown before in a colon carcinoma cell line and this is the first time that doxorubicin and FasL-induced apoptosis has been shown to be modulated by RKIP. Further, it is shown here, for the first time, that the modulation of chemotherapy-induced apoptosis by RKIP can change depending upon the cytotoxic drug employed as treatment. TRAIL and FasL, both members of the TNF super-family, were selected for further analysis due to the distinctive cell death responses observed as a consequence of the levels of RKIP within the cell. WT RKIP cells were sensitive to FasL treatment, and high RKIP cells were most sensitive to TRAIL administration. Increased sensitivity of high RKIP-expressing colon cells to TRAIL treatment appeared to involve up-regulation of the DR5 receptor; down-regulation of the anti-apoptotic molecule Bcl-xl; pIKK which activates the NF-κB pathway; and TRAF2 which has been shown to activate the NF-κB pathway. Whether RKIP directly interacts with these molecules is unknown however RKIP has been shown to bind upstream activators of the NF-κB pathway and another TRAF subtype TRAF6. YY1 expression was evident in the TRAIL-treated cells but the expression was unchanged as the levels of RKIP within the cell were altered. The FasL-treated cells also displayed decreased pIKK levels as the levels of RKIP were increased; it is possible that NF-κB was behaving as both pro- and anti-apoptotic within this cell line. Thus RKIP inhibition of the NF-κB pathway may have prevented FasL-induced apoptosis in the high RKIP-expressing colon carcinoma cells. The expression of TRAF6, which has been shown to bind RKIP, displayed a scaffold-like response with WT RKIP-expressing cells having the highest TRAF6 expression. This was also the case for the transcriptional regulator YY1, thus it is possible that both YY1 and TRAF6 were behaving in a pro-apoptotic-like manner in the WT RKIP-expressing cells. TRAF2 was also evident in the FasL-administered cells but the expression did not change regardless of the levels of RKIP within the cell. Overall, it appears that differential expression of TRAF adaptor proteins is responsible for the contrasting responses of TRAIL and FasL-treated cells with low, WT and high RKIP expression. Utilisation of particular TRAF adaptors or TRAF combinations by the TRAIL and Fas receptors may also account for the pro- and anti-apoptotic roles of the NF-κB pathway, and the recruitment or down-regulation of other proteins dependent upon the cell stimulus. How RKIP affects these proteins requires further investigation, however these results are exciting and novel, and strengthen evidence surrounding the role of RKIP in chemosensitivity. On another note, RKIP has been shown to bind the PDE5 inhibitor PF-3717842, therefore investigation of the effects of the PDE5 inhibitors sildenafil citrate and vardenafil citrate on RKIP inhibition of the ERK pathway in a colon carcinoma cell line were examined. The effects of the PDE5 inhibitors were compared to the cell migration inhibitor locostatin that has been shown to bind and inhibit RKIP, and prevent the RKIP-Raf-1 interaction. With TPA and EGF stimulation, locostatin appeared to act in a manner consistent with its known function as an RKIP inhibitor. The PDE5 inhibitors sildenafil citrate and vardenafil citrate displayed a similar trend to that of locostatin, although their effects on the ERK pathway were not as potent. It is possible that after EGF stimulation, the strong activation of B-Raf was over-shadowing the subtle effects of the drug treatments. Under growth conditions, the RKIP inhibitor locostatin did not appear to behave as an inhibitor of RKIP nor did the PDE5 inhibitors sildenafil citrate and vardenafil citrate. It is possible that the strong activation of various growth and proliferative cascades was impinging upon the ERK pathway, were overshadowing the drug effects, or resulting in off-target (RKIP-unrelated) effects of the drugs. In summary, the role of RKIP within the cell is becoming an increasingly exciting avenue of research and is consistently yielding new and interesting roles and interactions within the cell. Understanding and elucidating the roles of this intriguing protein within the cell will not only strengthen our knowledge of signal transduction regulation and modulation, but may also provide a new source of targeted therapy and means of manipulation in the treatment of cancer and chemotherapeutic drug resistance.
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Kurian, Stefanie [Verfasser]. "Effects of combination therapy of PDE5 inhibitor sildenafil and multikinase inhibitors sorafenib and sunitinib in NSCLC / Stefanie Kurian." Gießen : Universitätsbibliothek, 2015. http://d-nb.info/1076760546/34.

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Wang, Guocheng. "Design, synthesis and development of PDE5 inhibitors." Thesis, Aston University, 2009. http://publications.aston.ac.uk/15405/.

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This research project is concerned with the design, synthesis and development of new phosphodiesterase 5 (PDE5) inhibitors with improved selectivities and lower toxicities. Two series of a 5 member and a 6 member ring fused heterocyclic compounds were designed, and synthesized. By alteration of starting materials and fragments, two virtual libraries, each is consisted of close to hundred compounds, were obtained successfully. The screening of sexual stimulation activity with rabbits demonstrated both groups of compounds were able to stimulate rabbit penile erection significantly. The following toxicity studies revealed 2-(substituted-sulfonylphenyl)-imidazo [1,5-a]-1,3,5-triazine-4-(3H)-one group possessed an unacceptable toxicity with oral LD50 about 200mg/kg; while 2-(substituted-sulfonylphenyl)-pyrrolo[2,3-d]pyrimidin-4-one group showed an acceptable toxicity with oral LD50 over 2000mg/kg. The continued bioactivity studies showed yonkenafil, the representative of 2-(substituted-sulfonylphenyl)-pyrrolo[2,3-d]pyrimidin-4-one group, has a better selectivity towards PDE5 and PDE6 than sildenafil and a better overall profile of sexual stimulation on animals than sildenafil. Chronic toxicity studies of yonkenafil further confirmed yonkenafil did not cause any serious side effect and damage on animal models and most actions were explainable. Based on evidences of the above studies, yonkenafil were recommended to enter clinical trials by the regulation authority of China, SFDA. Currently yonkenafil has been through the Phase I clinical trials and ready to progress into Phase II. Hopefully, yonkenafil will provide an alternative to the ED patients in the future.
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Strange, Julian William Nevill. "PDE5 inhibition in pulmonary arterial hypertension." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441986.

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NGUYEN, HOANG OANH. "ANTI-INFLAMMATORY PROPERTIES OF PDE4 INHIBITION IN SARS-COV-2-ACTIVATED HUMAN DENDRITIC CELLS." Doctoral thesis, Università degli studi di Brescia, 2022. http://hdl.handle.net/11379/555422.

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È stato dimostrato che la risposta immunitaria disfunzionale e l’iper-infiammazione con conseguente tempesta citochinica giocano un ruolo chiave nello sviluppo di forme severe di malattia da Coronavirus 2019 (COVID-19). Tale condizione clinica suggerisce che l’eccessiva risposta immunitaria innata potrebbe scatenare una patologia immunitaria virus-dipendente. In questo lavoro, viene descritto un nuovo meccanismo di attivazione delle cellule dendritiche da parte del virus SARS-CoV-2. Nello specifico, sequenze di RNA del genoma virale sono in grado di attivare dei recettori endosomiali, in particolare il TLR7 e TLR8. L’attivazione di questi recettori da parte delle sequenze di RNA virale ha indotto in-vivo una forte infiammazione polmonare, come dimostrato dall’accumulo di mediatori pro-infiammatori e dall’infiltrato leucocitario, mentre in-vitro ha indotto una polarizzazione in senso Th1 ed un forte rilascio di interferoni e citochine pro-infiammatorie. Tanimilast è un nuovo inibitore selettivo della fosfodiesterasi 4, che viene assunto per via inalatoria, ed è impiegato in avanzati studi clinici per il trattamento della broncopneumopatia cronica ostruttiva e che potrebbe potenzialmente rivelarsi utile nel trattamento della polmonite da COVID-19. In questo progetto abbiamo visto come la potente attivazione delle cellule dendritiche da parte di sequenze di RNA del SARS-CoV-2 è stata notevolmente inibita dal trattamento con Tanimilast. Il trattamento con Tanimilast ha infatti causato una diminuzione del rilascio di citochine pro-infiammatorie (TNF-α e IL6) e chemochine (CCL3, CXCL9 e CXCL10), nonché alla riduzione del rilascio di citochine associate alla polarizzazione in senso Th1 (IL-12 ed Interferoni di tipo I). Tuttavia, il trattamento con Tanimilast non ha influito sull’espressione dei marker di maturazione quali CD83, CD86, MHC-II e CCR7. Coerentemente con ciò, il trattamento con Tanimilast non ha compromesso la capacità delle cellule dendritiche attivate di attivare i linfociti T CD4+, ma ha deviato la loro polarizzazione preferenzialmente verso un fenotipo Th2. Inoltre, Tanimilast ha inibito l’espressione di molecole MHC di classe I, limitando di conseguenza l’attivazione e il differenziamento dei linfociti T citotossici CD8+. Gli effetti immunomodulatori di Tanimilast sono stati ulteriormente confermati dalla sua capacità di promuovere il rilascio di molecole immunosoppressorie cAMP-dipendenti come IDO1, TSP1, VEGF-A e anfiregulina in cellule dendritiche stimolate con LPS. Queste cellule hanno anche fortemente over-espresso il CD141 e mostrato un incremento nella fagocitosi di cellule morte. Complessivamente, i nostri risultati indicano che Tanimilast promuove l’acquisizione di proprietà immunomodulatorie da parte delle cellule dendritiche mature, nonché un differente fenotipo semi-maturo associato ad una elevata sovra espressione del CD141. I dati permettono quindi di suggerire Tanimilast come un promettente farmaco immunomodulatorio per il trattamento di malattie immuno-mediate o infiammatorie, possibilmente includendo le polmoniti severe da COVID-19.
Dysfunctional immune response and hyper-inflammation with subsequent cytokine storm were shown to play a key role in the development of severe and fatal forms of Coronavirus disease 2019 (COVID-19). This clinical condition suggests that an overactive innate immune response may unleash virus-dependent immune pathology. Here, we described a novel mechanism of SARS-CoV-2-dependent activation of dendritic cells (DCs), based on the recognition of sequences of viral genomic ssRNA (SCV2-RNA) by endosomal pattern recognition receptors, namely TLR7 and TLR8. Importantly, SCV2-RNA recapitulated potent lung inflammation in vivo as shown by accumulation of proinflammatory mediators and immune cell infiltration; and induced a strong release of pro-inflammatory cytokines and Th1 polarization in vitro. Tanimilast is a novel and selective inhaled inhibitor of phosphodiesterases 4 that is in advanced clinical development for the treatment of chronic obstructive pulmonary disease and could prove beneficial in severe COVID-19 pneumonia. In our experimental setting, the potent activation of DCs by SCV2-RNA was severely blunted by Tanimilast, which decreased the release of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (CCL3, CXCL9, and CXCL10) and of Th1-polarizing cytokines (IL-12, type I IFNs). However, Tanimilast did not impair the acquisition of the maturation markers CD83, CD86, HLA-DR and CCR7. Consistent with this, Tanimilast did not reduce the capability of activated DCs to activate CD4+ T cells but skewed their polarization towards a Th2 phenotype. In addition, Tanimilast blocked the increase of HLA class I molecules and restrained the proliferation and activation of cytotoxic CD8+ T cells accordingly. The immune-modulatory effects of Tanimilast were further demonstrated by its capacity to enhance cAMP-dependent immunosuppressive molecules such as IDO1, TSP1, VEGFA and Amphiregulin in LPS-stimulated DCs. These cells also strongly upregulated CD141 and displayed increased uptake of dead cells. Altogether, our results indicate that Tanimilast induce mature DCs to acquire immunomodulatory properties as well as a distinct semi-mature phenotype, associated with the prominent expression of CD141, thus proposing Tanimilast as a promising immunomodulatory drug for the treatment in inflammatory or immune-mediated diseases, possibly including severe COVID-19 pneumonia.
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LI, HONGWU. "Phosphodiesterase 7(PDE7) inhibitors: a new target to treat drug addiction." Doctoral thesis, Università degli Studi di Camerino, 2015. http://hdl.handle.net/11581/401772.

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Drug addiction not only causes addicts health damage, but also leads serious social, economic and public health problems, which threaten our harmonious society. The neurobiological mechanism of drug addiction has not been fully elucidated that is still lack of ideal treatment and intervention models. Especially, relapse is a worldwide problem, the high relapse rate after detoxification treatment more than 95%. The nucleotide phosphodiesterase (PDE) type 7 family includes two members, PDE7A and PDE7B, which are cyclic-AMP-specific PDEs expressed in brain dopaminergic regions linked to addiction, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here we assessed the role of PDE7 in addiction by evaluating selective PDE7 inhibitors (PDE7i) Compound A and Compound B in rat models of durg self-administration and relapse to drug seeking by behavior test. Our results showed that PDE7 inhibition by Compound A or Compound B significantly reduced fixed-ratio 3 and progressive ratio nicotine self-administration. In preclinical model of relapse we found that Compound A and Compound B also attenuated cue- and yohimbine-induced reinstatement of nicotine seeking. In rats implanted bilaterally with intracranial cannulas aimed at the VTA, we found that site specific injection of Compound A or Compound B into this brain area significantly reduced nicotine self-administration under both FR-3 and PR schedule of reinforcement suggesting a role of corticomesolimbic dapaminergic circuitries in PDE7i effects. In cocaine addiction experiments, the results showed that PDE7 inhibitor Compound B (low dose, intermediate dose and high dose) significantly reduced cue-induced relapse to cocaine seeking. The reinstatement experiments showed that PDE7 inhibitor exhibited significant effects in preventing stress-induced relapse to cocaine seeking behavior at the doses tested (low dose and high dose). The same results were found in heroin addiction test. The PDE7 inhibitor Compound A (intermediate dose and high dose) significantly reduced heroin-seeking behavior after extinction. The reinstatement experiments showed that PDE7 inhibitor Compound A exhibited significant effects in preventing cue-induced relapse to heroin seeking behavior at the doses tested (low dose, intermediate dose and high dose). Further, PDE7 inhibitor (intermediate dose and high dose) significantly reduced alcohol self-administration. The reinstatement experiments showed that PDE7 inhibitor exhibited significant effects in preventing stress- and cue-induced relapse to alcohol seeking behavior. These findings suggest that PDE7 could be a novel therapeutic target for drug addiction.
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Tippelt, Sabine [Verfasser]. "Untersuchung der Pathogenese der möglicherweise speziesspezifischen toxikologischen Effekte von PDE4-Inhibitoren bei Ratten / Sabine Tippelt." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2013. http://d-nb.info/1037885198/34.

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Xu, Chenjia. "A Novel in vitro PDE7 Inhibitor Inhibits IL-2 Gene Expression in Activated T Cells and Induces Apoptosis in a B-cell Line and Monocytic Cell Line." Thesis, Boston College, 2013. http://hdl.handle.net/2345/3935.

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Thesis advisor: Thomas C. Chiles
Elevating intracellular cAMP levels can result in a wide range of anti-inflammatory effects and growth arrest and apoptosis in cancer cells, marking phosphodiesterases (PDEs) as potential targets for inflammatory diseases and cancer treatment. PDE7A is proposed to be a new therapeutic target for its ubiquitous expression in proinflammatory and immune cells. A Barbituric acid based compound, BC12 was identified as an in vitro PDE7 inhibitor in fission-yeast-based high-throughput screen. Analysis of this compound on the activation of Jurkat T lymphocytes, mouse and human primary T cells reveals inhibition of IL-2 production, though cell viability is not significantly impacted. Real-time RT-PCR and mRNA stability assays indicate that the inhibition of IL-2 production by BC12 is attributable to transcriptional repression without accelerating IL-2 mRNA decay. By contrast, compounds of similar structure with that of BC12 exhibit varying effects on IL-2 production that does not correlate with their in vitro PDE7 inhibitory activity, suggesting that the in vivo target of BC12 responsible for these effects may not be PDE7. Our study further reveals that BC12 inhibits IL-2 transcription through targeting NFAT and NFkB-mediated pathways. Preliminary investigation on other T helper cell cytokine secretion indicates that BC12 has a potential to selectively inhibit Th2 cytokines. Our data suggest that BC12 may present a novel anti-inflammatory drug for its immunosuppressive and potential immunomodulatory effects. Analysis of BC12 on a human B-cell line and a monocytic cell line demonstrate its pro-apoptotic effects in a dose-dependent manner. Titration of BC12 on human diffuse large B-cell lymphoma (DLBCL), LY18 cells, and human primary B cells reveals that BC12 induces cell death more effectively in DLBCL LY18 cells than normal B cells, suggesting the anti-cancer potential of this compound
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
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Grommel, Sonja [Verfasser]. "Untersuchung möglicher positiver Effekte hinsichtlich der Aufrechterhaltung der Gravidität durch PDE4-Inhibitoren an Ratten / Sonja Grommel." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2013. http://d-nb.info/1037800826/34.

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Clapham, John Christopher. "Characterisation and structural studies on dog heart cyclic nucleotide phosphodiesterase." Thesis, Birkbeck (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267913.

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Books on the topic "PDE4 inhibitor"

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Behrens, Frank, Michaela Koehm, and Michael J. Parnham. Synthetic DMARDs. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198737582.003.0028.

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Synthetic disease modifying anti-rheumatic drugs (sDMARDs) are first line systemic treatment options for management of active psoriatic arthritis (PsA). Most of the compounds are used based on evidence from clinical trials in rheumatoid arthritis and from experience in routine care. Methotrexate is often recommended as the first choice within among sDMARDs, despite controversial or missing evidence of efficacy, according to experience over many years. Leflunomide, sulfasalazine, and cyclosporin are additional established options to treat PsA. The recently approved PDE4 inhibitor, apremilast, has broad evidence of efficacy. All these drugs have different strengths and weaknesses and varying levels of evidence for treatment of PsA. Therefore, the best treatment choice must be based on the different individual manifestations of the disease and comorbid conditions. In this chapter, the evidence levels for the different clinical symptoms are listed and suggestions for a hierarchical order of choice are given, adapted to likely clinical scenarios.
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Porst, Hartmut. Erectile dysfunction. Edited by David John Ralph. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0103.

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Erectile dysfunction (ED) can be improved by changing certain lifestyle factors such as sedentary lifestyle, unhealthy food, nicotine and alcohol abuse, or optimal management of risk factors/concomitant diseases causing or aggravating ED such as dyslipidaemia, hypertension, diabetes mellitus, depression, BPH/LUTS, or hypogonadism.First choice in the medical therapy of ED are PDE-5 inhibitors such as sildenafil, vardenafil, and tadalafil used p.r.n, or on a daily low-dose regimen regarding tadalafil, especially in patients suffering from ED and BPH/LUTS. Yohimbine and L-arginine may be considered in patients with mild PE, which also applies for topical alprostadil. Both transurethral alprostadil and self-injection therapy with alprostadil, papaverine/phentolamine, or the trimix combination consisting of all three compounds is mostly reserved for those patients non-or poorly responding to PDE-5 inhibitors. Finally, combination therapy with PDE-5 inhibitors and transurethral alprostadil or intracavernous self-injection therapy can be able to rescue non-responders to either monotherapy.
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Book chapters on the topic "PDE4 inhibitor"

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McAllister-Williams, R. Hamish, Daniel Bertrand, Hans Rollema, Raymond S. Hurst, Linda P. Spear, Tim C. Kirkham, Thomas Steckler, et al. "PDE4 Inhibitors." In Encyclopedia of Psychopharmacology, 977. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1541.

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McAllister-Williams, R. Hamish, Daniel Bertrand, Hans Rollema, Raymond S. Hurst, Linda P. Spear, Tim C. Kirkham, Thomas Steckler, et al. "PDE3 Inhibitors." In Encyclopedia of Psychopharmacology, 976–77. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1540.

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McAllister-Williams, R. Hamish, Daniel Bertrand, Hans Rollema, Raymond S. Hurst, Linda P. Spear, Tim C. Kirkham, Thomas Steckler, et al. "PDE5 Inhibitors." In Encyclopedia of Psychopharmacology, 977. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1542.

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McAllister-Williams, R. Hamish, Daniel Bertrand, Hans Rollema, Raymond S. Hurst, Linda P. Spear, Tim C. Kirkham, Thomas Steckler, et al. "PDE Inhibitors." In Encyclopedia of Psychopharmacology, 976. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_3466.

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Petroianu, Georg, and Peter Michael Osswald. "Phosphodiesterase(PDE)-Inhibitoren." In Anästhesie in Frage und Antwort, 155–57. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-662-05715-5_54.

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Gresele, Paolo, Stefania Momi, and Emanuela Falcinelli. "Dipyridamole and PDE Inhibitors." In Platelets in Thrombotic and Non-Thrombotic Disorders, 1283–98. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-47462-5_86.

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Drobnis, Erma Z., and Ajay K. Nangia. "Phosphodiesterase Inhibitors (PDE Inhibitors) and Male Reproduction." In Impacts of Medications on Male Fertility, 29–38. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-69535-8_5.

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Padma-Nathan, Harin. "Sildenafil Citrate, the Classic PDE5 Inhibitor." In Oral Pharmacotherapy for Male Sexual Dysfunction, 65–83. Totowa, NJ: Humana Press, 2005. http://dx.doi.org/10.1385/1-59259-871-4:065.

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Jackson, Graham. "The Hemodynamics of Phosphodiesterase-PDE5 Inhibitors." In Heart Disease and Erectile Dysfunction, 131–37. Totowa, NJ: Humana Press, 2004. http://dx.doi.org/10.1007/978-1-59259-748-2_8.

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Francis, Sharron H., and Jackie D. Corbin. "Sildenafil, pharmacology of a highly selective PDE5 inhibitor." In Sildenafil, 15–33. Basel: Birkhäuser Basel, 2004. http://dx.doi.org/10.1007/978-3-0348-7945-3_2.

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Conference papers on the topic "PDE4 inhibitor"

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Chen, W., Z. Xu, H. Wee, G. S. Lewis, N. Olsen, J. Lin, and S. G. Zheng. "THU0097 Phosphodiesterases 4 (PDE4) inhibitor ameliorates experimental arthritis." In Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.4989.

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Takeda, K., Y. Shiraishi, J. Domenico, JE Loader, S. Sanjar, JJ Lucas, and EW Gelfand. "Combined Effects of the Phosphodiesterase Type 4 (PDE4) Inhibitor, Roflumilast, and the PDE5 Inhibitor, Tadalafil, in Allergen-Induced Airway Hyperresponsiveness (AHR)." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5717.

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Beretz, A., F. Lanza, A. Stierlé, and J.-P. Cazenave. "CYCLIC NUCLEOTIDE PHOSPHODIESTERASE INHIBITORS PREVENT AGGREGATION AND SECRETION OF HUMAN PLATELETS BY RAISING CYCLIC AMP AND REDUCING CYTOPLASMIC FREE CALCIUM MOBILIZATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643586.

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Drugs that raise platelet cyclic AMP (cAMP) are potent inhibitors of platelet activation. We have studied the effects of 5 inhibitors of cyclic nucleotide phosphodiesterase (PDE) of different chemical structures (quercetin, Ro 15-2041, HL-725, cilostamide and MY-5445), which are all potent inhibitors of platelet function. The concentrations that inhibit by 50 % crude cAMP-PDE activity (IC50) from human platelets are: 0.06 μM(HL-725), 0.15 μM(Ro 15-2041 ), 0.23 μM(cilostamide), 6.9 μM(MY-5445) and 44.4 μM(quercetin). We measured on the same preparation of washed human platelets loaded with quin2, the aggregation and the increase in intracellular Ca2+ ([Ca2+]i) induced by 5 μM ADP alone or in the presence of PDE inhibitors.PGE1 (2 nM) potentiates significantly (1.6 to 3.3 fold) the inhibitory effects of PDE inhibitors on [Ca2+]i rises and platelet aggregation. Adrenaline, an inhibitor of adenylate cylase, prevents the effect of PDE inhibitors on ADP-induced [Ca2+]i rise and platelet aggregation. These results suggest that these compounds inhibit [Ca2+]i mobilization and subsequent ADP-induced aggregation through a rise in cAMP, because both effects are potentiated by PGE1 and inhibited by adrenaline. The inhibitor concentrations which potentiate the action of PGE1, on [ Ca2+]i levels also potentiate the rise in platelet cAMP induced by PGE-<. These results suggest that PDE inhibitors inhibit platelet aggregation Ly raising cAMP levels and subsequently inhibiting [Ca2+]i mobilization.
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Bridgewood, C., R. Cuthbert, M. Wittmann, and D. McGonagle. "AB0054 Pde4 inhibitor attenuation of il-23 secretion from mononuclear cells." In Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.7287.

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Rheault, Tara, Thomas Bengtsson, and Kathleen Rickard. "Ensifentrine, a dual PDE3/PDE4 inhibitor, improves FEV1 regardless of smoking status or history of chronic bronchitis." In ERS International Congress 2020 abstracts. European Respiratory Society, 2020. http://dx.doi.org/10.1183/13993003.congress-2020.4786.

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Chapman, Richard W., Aileen House, Jennifer Richard, Xiomara Fernandez, Howard Jones, Dan Prelusky, James Lamca, et al. "Pharmacology Of SCH900182, A Potent, Selective Inhibitor Of PDE4 For Inhaled Administration." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a5671.

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Kistemaker, Loes E. M., Tjitske A. Oenema, Wim A. de Jager, I. Sophie T. Bos, Fabrizio Facchinetti, Gino Villetti, and Reinoud Gosens. "LATE-BREAKING ABSTRACT: The PDE4 inhibitor CHF-6001 and LAMAs cooperatively inhibit bronchoconstriction-induced remodeling in lung slices." In ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.oa1974.

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Lucci, Germano, Fabrizia Mariotti, Debora Santoro, Daniela Acerbi, Gianluigi Poli, and Marie-Anna Nandeuil. "Safety, tolerability and pharmacokinetics of CHF 6001, a novel selective inhaled PDE4 inhibitor, in healthy volunteers." In ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.pa4086.

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Knowles, RG, DI Ball, MH Gascoigne, C. Tralau-Stewart, and AT Nials. "In VivoCharacterisation of GSK256066, an Exceptionally High Affinity and Selective PDE4 Inhibitor Suitable for Topical Administration." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a4582.

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Kubera, JE, FJ Schlerman, KH Nocka, RM Greco, CM Williams, and JP Sypek. "Characterization of Anti-Inflammatory Effects of a PDE4 Inhibitor in a Model of Acute Smoke Exposure." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5641.

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Reports on the topic "PDE4 inhibitor"

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Are all PDE5 inhibitors the same? BJUI Knowledge, March 2018. http://dx.doi.org/10.18591/bjuik.0470.

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Medical management of priapism, with a focus on PDE5 inhibitors. BJUI Knowledge, January 2016. http://dx.doi.org/10.18591/bjuik.0610.

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