Extracellular purines act via P1 and P2 receptors on podocytes and may influence on their function. This action may be modified under various (patho)physiological conditions leading to development of podocytopathy. Aim of study was to investigate effects of diabetic milieu, represented by high glucose concentration (HG, 30 mM glucose) on purinergic-induced changes of 2-deoxy-D-glucose (2-DG) uptake and on extracellular purines metabolism in cultured rat podocytes. Basal 2-DG uptake was 2.7-fold enhanced in HG compared to normal glucose concentration, NC (1271 +/- 86 vs. 477 +/- 37 nmol/h/mg protein, P < 0.001). ATP stimulated 2-DG uptake by 44 +/- 4% and 29 +/- 5% in NC and HG, respectively. ATP analogues, beta, gamma-methylene ATP and 2-methylthio ATP stimulated 2-DG uptake in range of 18-34% in NC and 16-17% in HG. Benzoylbenzoyl ATP increased 2-DG uptake about 24 +/- 2% in NC however, its effect in HG reached 50 +/- 1%. The antagonists of P2 receptors (suramin, reactive blue 2, PPADS) decreased basal 2-DG uptake in NC and HG; suramin and reactive blue 2 at average of 15 4% in NC but in HG the effect was in following order: suramin 28 +/- 3%; PPADS 20 +/- 3% and RB-2 9 +/- 0.9%. Extracellular adenosine concentration was higher in HG than in NC (0.48 +/- 0.01 vs. 5.05 +/-0.39 mu M, P < 0.05), however intracellular ATP content and extracellular ATP concentration were not affected. Neither ecto-ATPase nor ecto-5'-nucleotidase activities were affected in FIG. In conclusion, diabetic milieu affects purinergic modulation of glucose transport into podocytes which may play a role in development of diabetic podocytopathy. (C) 2010 Elsevier Inc. All rights reserved.