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- Title
Antiplatelet Effects of Selected Xanthine-Based Adenosine A 2A and A 2B Receptor Antagonists Determined in Rat Blood.
- Authors
Kubacka, Monika; Mogilski, Szczepan; Bednarski, Marek; Pociecha, Krzysztof; Świerczek, Artur; Nicosia, Noemi; Schabikowski, Jakub; Załuski, Michał; Chłoń-Rzepa, Grażyna; Hockemeyer, Jörg; Müller, Christa E.; Kieć-Kononowicz, Katarzyna; Kotańska, Magdalena
- Abstract
The platelet aggregation inhibitory activity of selected xanthine-based adenosine A2A and A2B receptor antagonists was investigated, and attempts were made to explain the observed effects. The selective A2B receptor antagonist PSB-603 and the A2A receptor antagonist TB-42 inhibited platelet aggregation induced by collagen or ADP. In addition to adenosine receptor blockade, the compounds were found to act as moderately potent non-selective inhibitors of phosphodiesterases (PDEs). TB-42 showed the highest inhibitory activity against PDE3A along with moderate activity against PDE2A and PDE5A. The antiplatelet activity of PSB-603 and TB-42 may be due to inhibition of PDEs, which induces an increase in cAMP and/or cGMP concentrations in platelets. The xanthine-based adenosine receptor antagonists were found to be non-cytotoxic for platelets. Some of the compounds showed anti-oxidative properties reducing lipid peroxidation. These results may provide a basis for the future development of multi-target xanthine derivatives for the treatment of inflammation and atherosclerosis and the prevention of heart infarction and stroke.
- Subjects
BLOOD platelet aggregation; MYOCARDIAL infarction; ADENOSINES; THROMBIN receptors; XANTHINE; RATS; PHOSPHODIESTERASES; BLOOD platelets
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 17, p13378
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241713378