Glomerular thromboxane A2/prostaglandin H2 receptors: characterization and effect of adriamycin-induced nephrotic syndrome

Biochim Biophys Acta. 1993 Apr 30;1181(2):148-54. doi: 10.1016/0925-4439(93)90104-9.

Abstract

We have characterized the thromboxane (TX) A2/prostaglandin (PG) H2 receptor in glomeruli isolated from the rat using the agonist radioligand [125I]-BOP. Binding of [125I]-BOP was highly specific, stereoselective, and to a single class of high affinity binding sites (Kd = 1.16 +/- 0.22 nM and Bmax = 348 +/- 32 fmol/mg protein; n = 6). Binding of [125I]-BOP was competed for by the agonist ONO11113 (Kd = 50.8 +/- 8.0 nM; n = 4) and the antagonists SQ29548 (Kd = 15.8 +/- 1.0 nM; n = 3), L657925 (Kd = 12.1 +/- 2.2 nM; n = 3) and L657926 (Kd = 1642 +/- 135 nM; n = 3). I-BOP also produced a TXA2/PGH2 receptor-mediated rise in [Ca2+]i in isolated glomeruli In adriamycin-induced nephrotic syndrome in the rat, the development of proteinuria is reported to be dependent on increased renal TXA2 production. We therefore examined whether or not changes in glomerular TXA2/PGH2 receptors occur between control and nephrotic rats. No changes in expression or affinity of either glomerular or platelet TXA2/PGH2 receptors were observed. Kd and Bmax 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 fmol/mg for nephrotic rats (n = 6).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Bridged Bicyclo Compounds / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Doxorubicin / toxicity*
  • Fatty Acids, Unsaturated / pharmacology
  • Kidney Glomerulus / metabolism*
  • Kinetics
  • Male
  • Nephrotic Syndrome / chemically induced
  • Nephrotic Syndrome / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / drug effects
  • Receptors, Prostaglandin / metabolism*
  • Receptors, Thromboxane / antagonists & inhibitors
  • Receptors, Thromboxane / drug effects
  • Receptors, Thromboxane / metabolism*
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology

Substances

  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Fatty Acids, Unsaturated
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • Receptors, Thromboxane A2, Prostaglandin H2
  • 7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid
  • Thromboxane A2
  • Doxorubicin
  • STA 2