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 microM) were prevented by a nonselective P2 receptor antagonist, that is, suramin (10 microM) and P2Y receptor antagonist - reactive blue 2 (50 microM). However, the antagonist of P1 receptor, that is, theophylline (1 microM) and A(1) receptor 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 microM) 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 microM). However, theophylline and the specific antagonist of A(2) receptor - 3,7-dimethyl-1-propargylxanthine (DMPX; 10 microM) - 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.
Szczepańska-Konkel
Miroslawa
M
Laboratory of Monitoring Therapy and Pharmacogenetics, Medical University of Gdansk, Debinki 7, 80-211 Gdansk, Poland.
Jankowski
Maciej
M
Stiepanow-Trzeciak
Anna
A
Angielski
Stefan
S
D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D015226:Dinucleoside Phosphates