The effect of quercetin on reperfusion-induced damage of myocardium

Abstract

Adenosine is a key metabolite in myocardial autoregulation and interactions between different types of cells in its production, metabolism and action are vital. In this study, adenosine and other purine catabolite production were analyzed in cultured umbilical vein endothelial cells under control conditions (normal O2 and substrate supply) and with inhibitors of ATP formation (iodoacetate and oligomycin -1 + O). Innhhibitors of adenosine deaminase - erythro-9 (2-hydroxy-3-nonyl) adenine (EHNA) and adenosine kinase 5´ iodotubercidin (ITu) were included where indicated. Nucleotides and catabolites were evaluated by HPLC in the cells and in the medium throughout 45 min of incubation at 370C. Total amounts or increments per culture flask (n = 4-5, ± SEM) were as follows: In controls with EHNA, cellular ATP, ADP and AMP contents were 9.0 ± 0.1, 0.83 ± 0.14 and 0.15 ± 0.03 nmol, while in the medium increases in hypoxanthine, xanthine and uric acid content were 1.0 ± 0.2, 0.4 ± 0.1 nmol and 0.5 ± 0.2 nmol. Adenosine increased by -/006 ± 0.04 nmol. With additional presence of ITu, adenosine rose by 0.9 ± 0.2 nmol (p<0.005). After 45 min incubation with I+O and EHNA, ATP was totally depleted, cellular AMP rose to 3.0 ± 1.2 nmol and no IMP increase was found. Medium adenosine rose by 5.6 ± 0.2 nmol and the increase in sum of other purine catabolites was 2.8 ± 03 nmol. In conclusion, adenosine formed in the endothelial cells under normal O2 and substrate supply is recycled via adenosine kinase. In ATP depleted cells, nucleotide catabolism proceeds predominantly via adenosine.