Effects of diadenosine polyphosphates on glomerular volume

1 Diadenosine polyphosphates (P 1 ,P 3 ‐diadenosine triphosphate, Ap 3 A; P 1 ,P 4 ‐diadenosine tetraphosphate, Ap 4 A; and P 1 ,P 5 ‐diadenosine pentaphosphate, Ap 5 A) are vasoactive molecules. The experimental model of isolated rat renal glomeruli was used to investigate their effects on glomerular vasculature. We measured the changes of glomerular inulin space (GIS) as a marker of glomeruli contractility. 2 Ap 4 A and Ap 5 A induced concentration‐ and time‐dependent reduction of GIS whereas Ap 3 A had no effect. The effects of Ap 4 A and Ap 5 A (both at 1  μ M ) were prevented by a nonselective P2 receptor antagonist, that is, suramin (10  μ M ) and P2Y receptor antagonist – reactive blue 2 (50  μ M ). However, the antagonist of P1 receptor, that is, theophylline (1  μ M ) and A 1 receptor 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX; 10  μ M ) did not affect the responses of glomeruli to Ap 4 A or Ap 5 A. 3 Ap 3 A, in contrast to Ap 4 A and Ap 5 A, prevented angiotensin II‐induced reduction of GIS in a concentration‐ and time‐dependent manner. This effect was partially prevented by suramin and markedly reduced by reactive blue 2 and the specific antagonist of P2Y 1 receptor – MRS 2179 (10  μ M ). However, theophylline and the specific antagonist of A 2 receptor – 3,7‐dimethyl‐1‐propargylxanthine (DMPX; 10  μ M ) – did not affect Ap 3 A action. 4 We indicate that diadenosine polyphosphates changed the glomerular volume via activation of P2 receptors. We suggest that extracellular Ap 4 A and Ap 5 A via P2X and P2Y receptors may decrease and Ap 3 A via , at least in part, P2Y 1 receptors may increase filtration surface, which in turn may modify glomerular filtration rate.British Journal of Pharmacology (2005) 144 , 1109–1117. doi: 10.1038/sj.bjp.0706149