ArticleBritish journal of pharmacology2008
Short-term or long-term treatments with a phosphodiesterase-4 (PDE4) inhibitor result in opposing agonist-induced Ca(2+) responses in endothelial cells.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- Single-nucleotide polymorphism rs2910829 inOpen life sciences · 2024Article
- GαFrontiers in pharmacology · 2022Review
- Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue.Biomedicines · 2021Review
- PDE4 inhibition as a therapeutic strategy for improvement of pulmonary dysfunctions in Covid-19 and cigarette smoking.Biochemical pharmacology · 2021Review
- Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium.Journal of the American College of Cardiology · 2019Article
- Inhibition of TPL2 by interferon-α suppresses bladder cancer through activation of PDE4D.Journal of experimental & clinical cancer research : CR · 2018Article
- Dexamethasone Inhibits Synergistic Induction of PDE4B Expression by Roflumilast and Bacterium NTHi.International journal of molecular sciences · 2018Article
- Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages.Journal of neuroinflammation · 2017Article
- Cross-talk between PKA-Cβ and p65 mediates synergistic induction of PDE4B by roflumilast and NTHi.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.Brain, behavior, and immunity · 2014Article
- Effects of PDE4 pathway inhibition in rat experimental stroke.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- Downregulation of brain phosphodiesterase type IV measured with 11C-(R)-rolipram positron emission tomography in major depressive disorder.Biological psychiatry · 2012Article
- Postinjury treatment with rolipram increases hemorrhage after traumatic brain injury.Journal of neuroscience research · 2012Article
- Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments.British journal of pharmacology · 2012Review
- Article
- Concerted regulation of cGMP and cAMP phosphodiesterases in early cardiac hypertrophy induced by angiotensin II.PloS one · 2010Article
- Characterization of novel phosphodiesterases in the bovine ovarian follicle.Biology of reproduction · 2009Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeWe previously reported that agonist-induced rises in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in human umbilical vein endothelial cells (HUVEC) were inhibited after a short-term (2 min) pre-treatment with cAMP-elevating agents. The aim of this work was to study the effects of longer term (8 h) pre-treatment with dibutyryl-cAMP (db-cAMP) or rolipram, a specific inhibitor of phosphodiesterase-4 (PDE4), on [Ca(2+)](i), cAMP levels and PDE activity and expression in HUVEC. EXPERIMENTAL APPROACH: [Ca(2+)](i) changes were measured in isolated HUVEC by Fura-2 imaging. Intracellular cAMP levels and PDE4 activity were assessed by enzyme-immunoassay and radio-enzymatic assay, respectively. PDE expression was measured by northern and western blot analysis. KEY
resultsLong-term pre-treatment of HUVEC with rolipram or db-cAMP significantly increased ATP-, histamine- and thrombin-induced [Ca(2+)](i) rises. Short-term pre-treatment with rolipram was associated with an increase in cAMP, whereas long-term pre-treatment was associated with a decrease in cAMP. Long-term pre-treatment with rolipram or db-cAMP induced a significant increase in PDE4 activity and the expression of 74 kDa-PDE4A and 73 kDa-PDE4B was specifically enhanced. All these effects were suppressed by cycloheximide. CONCLUSIONS AND IMPLICATIONS: Our data suggest that sustained inhibition of PDE4 by rolipram induced an increase in PDE4 activity, possibly as a compensatory mechanism to accelerate cAMP degradation and that PDE4A and PDE4B were implicated in the regulation of [Ca(2+)](i). Thus, isozyme-specific PDE4 inhibitors might be useful as therapeutic agents in diseases where [Ca(2+)](i) handling is altered, such as atherosclerosis, hypertension and tolerance to beta-adrenoceptor agonists.
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