P0999URINARY EXCRETION OF ADENYLATE AND URIDYLATE NUCLEOTIDES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Abstract

Abstract Background and Aims Extracellular nucleotides (ATP, ADP, UTP, UDP) acting through P2-receptors regulate renal vascular tone and glomerular permeability tor albumin. Both phenomenons are dysregulated in diabetes and are conducive to development of diabetic nephropathy. The aim of study was to investigate the urinary excretion of adenylate and uridynate nucleotides and the effects of suramin, P2-receptors antagonist and non-competitive inhibitor of ectoATPase, on those parameters in streptozotocin-induced diabetic rats. Method Diabetes in Wistar rats was induced by streptozotocin injection (65 mg/kg, i.p, day 0) and suramin was injected (10 mg/kg, i.p) on day 7 and 14. Nucleotides concentration in urine collected in metabolic cages on day 21 (3-weeks diabetes) were measured using HPLC method wit UV detector. All values are expressed as mean ± SEM. Results The excretion of ATP, UTP, ADP and UDP in diabetes were increased i.e. ATP: 34.99±1.73 vs 18.56±1.59 μmol/24h (p<0.001); UTP: 0,72±0.06 vs 0.47±0,08 vs μmol/24h (p=0.03); ADP: 0,70±0.56 vs 0.28±0,04 vs μmol/24h (p=0.001); UDP: 9.08±1.28 vs 5.06±0,83 vs μmol/24h (p=0.02). UMP excretion was decreased 7.04±0.89 vs 11.36±0,621 μmol/24h (p=0.002) but AMP excretion was not affected by diabetes i.e. 0.86±0.09 vs 0.89±0.12 μmol/24h (p=0.08). Suramin administration did not affect urinary excretion of investigated nucleotides. Conclusion diabetes increases the urinary excretion of ATP, ADP, UTP and UDP and this effect is not modified by suramin. The changes in extracellular metabolism of nucleotides may affect the renal function during diabetes. This work was supported by National Science Centre Poland Grant (2016/23/B/NZ5/02632) to MJ.