Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the postischemic alterations in dopamine D1 receptor and Ca2+/calmodulin independent cyclic adenosine monophosphate (cyclic AMP) selective phosphodiesterase in gerbils and examined the effect of pentobarbital on these alterations. [3H]SCH 23390 and [3H]rolipram, respectively, were used to label dopamine D1 receptor and Ca2+/calmodulin independent cyclic-AMP selective phosphodiesterase. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min prior to ischemia. 5 h after ischemia, [3H]rolipram binding decreased significantly in the striatum and hippocampus, whereas no significant change was found in [3H]SCH 23390 binding. 7 days after ischemia, however, there was a marked reduction in both [3H]SCH 23390 and [3H]rolipram binding in the striatum and hippocampus, where histological neuronal damage was found. Pentobarbital significantly ameliorated postischemic decreases in [3H]rolipram binding both 5 h and 7 days after recirculation in most areas studied. Furthermore, this drug significantly prevented postischemic reduction in [3H]SCH 23390 binding (only) 7 days after ischemia. These results suggest that alteration of cyclic AMP selective phosphodiesterase is more sensitive at an earlier stage after ischemic insult than that of dopamine D1 receptors. Our results also demonstrate that pentobarbital reduces the alteration in [3H]SCH 23390 and [3H]rolipram binding after cerebral ischemia.
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PMID:Effect of pentobarbital on postischemic SCH 23390 and rolipram binding in gerbil brain. 822 65

Recent findings suggests that PDE4D (gene encoding phosphodiesterase 4D) is a stroke-related gene in the Icelandic population, but it is still very controversial as to whether it is a susceptible gene for stroke in other populations. In the present study, we attempted to explore the role of the gene in the pathogenesis of stroke in the Chinese Han population of eastern China. A total of 649 ischaemic stroke patients and 761 unrelated control individuals with no history of stroke or transient ischaemic attack were examined in a case-control study. Four SNPs (single nucleotide polymorphisms) rs152312 (C/T), SNP56 (A/T), SNP83 (C/T) and SNP87 (C/T) with a minor allele frequency over 5% were genotyped and the corresponding haplotypes were constructed. In an analysis of the combined cardiogenic and carotid stroke group, both the allele (P=0.0060) and genotype (P=0.0160) frequencies between cases and controls at SNP83 showed significant differences. However, no difference in haplotype frequencies was observed between cases and controls at rs152312 and SNP56. In the analysis of the small-artery-occlusive stroke group, no difference in allele or genotype frequencies was observed at any marker between cases and controls; the global haplotype frequency in rs152312 and SNP56 had a significant difference between cases and controls (P=0.0162); the frequency of haplotype C-A was higher in cases than in controls (P=0.0122). In conclusion, our present findings show that polymorphisms in the PDE4D gene are associated with an increased risk of ischaemic stroke in the Chinese Han population. The present study adds further support to the role of PDE4D in stroke.
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PMID:Association between the PDE4D gene and ischaemic stroke in the Chinese Han population. 1919 40

The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combination of aspirin plus dipyridamole are widely used for primary (in high-risk patients) and secondary prevention of atherosclerotic diseases. Research of new pharmacological strategies is driven by the need to reduce the risk of bleeding associated with the use of antiplatelet drugs. In this context cilostazol, a type III phosphodiesterase inhibitor, has demonstrated antiplatelet and vasodilator effects with low rate of bleeding complications. This review will focus on the pharmacological properties of cilostazol and its use in the management of atherothrombotic vascular diseases.
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PMID:Cilostazol in the management of atherosclerosis. 2018 Jul 73

Antiplatelet therapy is indicated in patients with non-cardioembolic stroke. The clinically used antiplatelet agents for secondary stroke prevention in this group of patients include the cyclooxygenase-1 (COX-1) inhibitor aspirin, the ADP receptor (P2Y12) inhibitors clopidogrel and ticlopidine, and the phosphodiesterase (PDE) inhibitors cilostazol and dipyridamole. Per medical economic data, aspirin is the most widely used antiplatelet agent. However, its use affords modest reduction in the risk of stroke recurrence and increases the risk of hemorrhagic stroke. The CSPS2 showed that the incidence of stroke recurrence was lower in patients receiving cilostazol than in those receiving aspirin. Furthermore, it showed that the incidence of intra- or extracranial hemorrhage requiring hospitalization in cilostazol-treated patients was approximately half of that in aspirin-treated patients. The study also showed that the incidence of hemorrhagic stroke was significantly lower in patients receiving cilostazol than in those receiving aspirin. Meta-analysis of the CARESS and CLAIR studies showed a significant reduction of microembolic signals (MES) on transcranial Doppler (TCD) monitoring by dual antiplatelet therapy (DAPT) with aspirin and clopidogrel than treatment with aspirin alone in patients who experienced a transient ischemic attack (TIA) or stroke with extra- or intracranial artery stenosis and MES positivity. The CHANCE study conducted in China showed a lower incidence of ischemic stroke in DAPT-treated patients than in those treated with aspirin monotherapy, while the incidence of hemorrhagic stroke was similar between the 2 treatment groups. However, DAPT should be restricted in the acute phase of stroke or TIA in acute settings. Novel antiplatelet agents have been developed for stroke prevention, and large randomized clinical trials should be conducted to evaluate the efficacy and safety of these agents when used singularly or in combination.
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PMID:[Antiplatelet therapy: update in secondary stroke prevention]. 2383 80

Dipyridamole is a platelet inhibitor indicated for the secondary prevention of transient ischemic attack. It inhibits the enzyme phosphodiesterase, elevates cAMP and cGMP levels and prevents platelet aggregation. Dipyridamole inhibits the cellular uptake of adenosine into red blood cells, platelets and endothelial cells that results in increased extracellular availability of adenosine, leading to modulation of cardiovascular function. The antiplatelet action of dipyridamole might offer therapeutic benefits in secondary stroke prevention in combination with aspirin. Inflammation and oxidative stress play an important role in atherosclerosis and thrombosis development, leading to stroke progression. Studies demonstrated anti-inflammatory, anti-oxidant and anti-proliferative actions of dipyridamole. These pleiotropic potentials of dipyridamole might contribute to improved therapeutic outcomes when used with aspirin in preventing secondary stroke. Dipyridamole was documented as a coronary vasodilator 5 decades ago. The therapeutic failure of dipyridamole as a coronary vasodilator is linked with induction of 'coronary steal' phenomenon in which by dilating resistance vessels in non-ischemic zone, dipyridamole diverts the already reduced blood flow away from the area of ischemic myocardium. Dipyridamole at high-dose could cause a marked 'coronary steal' effect. Dipyridamole, however, at low-dose could have a minimal hemodynamic effect. Low-dose dipyridamole treatment has a therapeutic potential in partially preventing diabetes mellitus-induced experimental vascular endothelial and renal abnormalities by enhancing endothelial nitric oxide signals and inducing renovascular reduction of oxidative stress. In spite of plenteous research on dipyridamole's use in clinics, its precise clinical application is still obscure. This review sheds lights on pleiotropic pharmacological actions and therapeutic potentials of dipyridamole.
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PMID:Classical and pleiotropic actions of dipyridamole: Not enough light to illuminate the dark tunnel? 2486 66