Abstract
Phosphodiesterases (PDEs) represent a super-family of 11 enzymes hydrolyzing cyclic nucleotides into inactive 5′ monophosphates. Inhibition of PDEs leads to a variety of cellular effects, including airway smooth muscle relaxation, inhibition of cellular inflammation, and immune responses. In this study we focused on theophylline, a known non-selective inhibitor of PDEs. Theophylline has been used for decades in the treatment of chronic inflammatory airway diseases. It has a narrow therapeutic window and belongs to the drugs whose plasma concentration should be monitored. Therefore, the main goal of this study was to evaluate the plasma theophylline concentration and to determine its relevance to pharmacological effects after single and longer term (7 days) administration of theophylline at different doses (5, 10, 20, and 50 mg/kg) in guinea pigs. Airway hyperresponsiveness was assessed by repeated exposure to ovalbumin. Theophylline reduced specific airway resistance in response to histamine nebulization, measured in a double chamber body plethysmograph. A decrease in tracheal smooth muscle contractility after cumulative doses of histamine and acetylcholine was confirmed in vitro. A greater efficacy of theophylline after seven days long treatment indicates the predominance of its anti-inflammatory activity, which may be involved in the bronchodilating action.
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Acknowledgments
This work was supported by the Slovak Research and Development Agency under the contract No. APVV-0305-12, by grant MZ 2012/35-UKMA-12, grant VEGA 1/0260/14, CEKR 2, and by project UK/131/2015.
This work was supported by the project “Biomedical Center Martin”, ITMS code: 26220220187, the project is co-financed from EU sources.
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The authors declare no conflicts of interest in relation to this article.
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Urbanova, A. et al. (2016). Bronchodilator and Anti-Inflammatory Action of Theophylline in a Model of Ovalbumin-Induced Allergic Inflammation. In: Pokorski, M. (eds) Pulmonary Infection and Inflammation. Advances in Experimental Medicine and Biology(), vol 935. Springer, Cham. https://doi.org/10.1007/5584_2016_31
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DOI: https://doi.org/10.1007/5584_2016_31
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