GLOMERULAR THROMBOXANE-A(2) PROSTAGLANDIN H(2)-RECEPTORS - CHARACTERIZATION AND EFFECT OF ADRIAMYCIN-INDUCED NEPHROTIC SYNDROME

We have characterized the thromboxane (TX) A2/prostaglandin (PG) H-2 r eceptor in glomeruli isolated from the rat using the agonist radioliga nd [I-125]-BOP. Binding of [I-125]-BOP was highly specific, stereosele ctive, and to a single class of high affinity binding sites (K(d) = 1. 16 +/- 0.22 nM and B(max) = 348 +/- 32 fmol/mg protein; n = 6). Bindi ng of [I-125]-BOP was competed for by the agonist ONO11113 (K(d) = 50. 8 +/- 8.0 nM; n = 4) and the antagonists SQ29548 (K(d) = 15.8 +/- 1.0 nM; n = 3), L657925 (K(d) = 12.1 +/- 2.2 nM; n = 3) and L657926 (K(d) = 1642 +/- 135 nM; n = 3). I-BOP also produced a TXA2/PGH2 receptor-me diated rise in [Ca2+]i in isolated glomeruli In adriamycin-induced nep hrotic syndrome in the rat, the development of proteinuria is reported to be dependent on increased renal TXA2 production. We therefore exam ined whether or not changes in glomerular TXA2/PGH2 receptors occur be tween control and nephrotic rats. No changes in expression or affinity of either glomerular or platelet TXA2/PGH2 receptors were observed. K (d) and B(max) values for isolated glomeruli were 1.45 +/- 0.24 nM and 406 +/- 72 fmol/mg for controls and 1.22 +/- 0.25 nM and 321 +/- 62 f mol/mg for nephrotic rats (n = 6).