In this study, the effects of diadenosine polyphosphates on kidney function were examined. Intravenous application of diadenosine hexaphosphate (AP6A) led to a significant threefold increase in both urine flow (from 2.45 +/- 0.2 to 13.8 +/- 0.74 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.41 +/- 0.12 to 1.52 +/- 0.28 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). In contrast, diadenosine triphosphate dose-dependently reduced urine flow (from 3.74 +/- 0.3 to 2.57 +/- 0.1 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.45 +/- 0.1 to 0.13 +/- 0.1 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). ATP and the P2y purinoceptor agonist gamma-S-ATP did not significantly modulate urine flow and Na+ excretion. alpha, beta-methylene-ATP, a P2x purinoceptor agonist, significantly increased urine flow from 1.74 +/- 0.5 to 4.07 +/- 1.51 microL/min per 100 g body wt, whereas Na+ excretion was unaffected. The effects were independent of alterations in GFR. Pretreatment with indomethacin (2.0 mg/kg body wt iv) completely abolished the effects of AP6A on urine flow and Na+ excretion. Similarly, pretreatment with the endothelin antagonist bosentan abolished the effects of AP6A on both urine flow and Na+ excretion, whereas suramin had no effects on the AP6A-induced increase in urine flow. In conclusion, diadenosine polyphosphates exert specific actions on urine flow and Na+ excretion that are different from the effects of ATP. AP6A may partially influence renal function by stimulating prostaglandin and endothelin release.
