RT Journal Article SR Electronic T1 KD-64 – a new selective A2A adenosine receptor antagonist has anti-inflammatory activity but contrary to the non-selective antagonist – caffeine does not reduce diet-induced obesity in mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.17.952531 DO 10.1101/2020.02.17.952531 A1 Magdalena Kotańska A1 Anna Dziubina A1 Małgorzata Szafarz A1 Kamil Mika A1 Karolina Reguła A1 Marek Bednarski A1 Małgorzata Zygmunt A1 Anna Drabczyńska A1 Jacek Sapa A1 Katarzyna Kieć-Kononowicz YR 2020 UL http://biorxiv.org/content/early/2020/02/17/2020.02.17.952531.abstract AB The A2 adenosine receptors play an important role, among others, in the regulation of inflammatory process and glucose homeostasis in diabetes and obesity. Thus, the presented project evaluated of influence of the selective antagonist of A2A adenosine receptor – KD-64 as compared to the known non-selective antagonist – caffeine on these two particular processes. Two different inflammation models were induced namely local and systemic inflammation. Obesity was induced in mice by high-fat diet and the tested compounds (KD-64 and caffeine) were administrated for 21 days. KD-64 showed anti-inflammatory effect in both tested inflammation models and administered at the same dose as ketoprofen exerted stronger effect than this reference compound. Elevated levels of IL-6 and TNF-α observed in obese control mice were significantly lowered by the administration of KD-64 and were similar to the values observed in control non-obese mice. Interestingly, caffeine increased the levels of these parameters. In contrast to caffeine which had no influence on AlaT activity, KD-64 administration significantly lowered AlaT activity in the obese mice. Although, contrary to caffeine, KD-64 did not reduce diet-induced obesity in mice, it improved glucose tolerance. Thus, the activity of the selective adenosine A2A receptor antagonist was quite different from that of the non-selective.