Renal thromboxane(Tx) production is increased in the MRL-/pr murine model of lupus nephritis. To investigate the relationship between increased Tx production and number and affinity of Tx receptors, we measured binding of the Tx receptor antagonist [3H][5Q295481 Si a, 2/3 (5Z), 3/3, 4a]-7-(3-((2-((phenyl-amino)-carbonyl) hydrozino) methyl)-7-oxabicyclo-(2.2. 1) heptan-2-yl)-5-heptenoic acid in glomerular preparations from MRL-/pr mice and both MRL-+/+ and LG/J controls. Renal Tx binding was first characterized in normal LG/J mice. In these animals, gbmerular binding was specific, saturable and reversible. Scatchard analysis revealed a single class of high-affinity binding sites. We next evaluated Tx production and binding in 12-and 16-weekold MRL-lpr mice and MRL-+/+ controls. To assess renal Tx production, excretion of TxB2 was measured in urine. Urinary

TxB2 was increased in MRL-Ipr mice at 16 weeks of age. This increase in urinary TxB2 was associated with a reduction in density of gbomerular Tx binding sites compared to either 12-week-old MRL-Ipr mice or MRL-+/+ controls. Ligand binding affinity was similar in all groups. To investigate if this alteration in binding was specific for Tx, glomerular binding of [3H} angio-tensin II was measured. In MRL-lpr mice, the number and affinity of gbomerular angiotensin binding sites were similar at 12 and 16 weeks of age. Thus, in this murine model of lupus nephritis, enhanced renal Tx production is temporally associated with a decrease in glomerular Tx binding sites without a change in receptor affinity. We speculate that alterations in Tx receptor number may be an important mechanism for modulating physiologic responses to Tx in the kidney.