Characterization of glomerular thromboxane receptors in murine lupus nephritis.
Renal thromboxane (Tx) production is increased in the MRL-lpr 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][SQ295481S-1 alpha,2 beta(5Z),3 beta,4 alpha]-7-(3-((2-((phenyl- amino)-carbonyl)hydrozino)methyl)-7-oxabicyclo-(2.2.1)heptan -2-yl)-5-heptenoic acid in glomerular preparations from MRL-lpr mice and both MRL(-)+/+ and LG/J controls. Renal Tx binding was first characterized in normal LG/J mice. In these animals, glomerular 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-week-old MRL-lpr mice and MRL(-)+/+ controls. To assess renal Tx production, excretion of TxB2 was measured in urine. Urinary TxB2 was increased in MRL-lpr mice at 16 weeks of age. This increase in urinary TxB2 was associated with a reduction in density of glomerular Tx binding sites compared to either 12-week-old MRL-lpr 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]angiotensin II was measured. In MRL-lpr mice, the number and affinity of glomerular 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Spurney
R F
RF
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Onorato
J J
JJ
Ruiz
P
P
Pisetsky
D S
DS
Coffman
T M
TM
D000818:Animals; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D017482:Receptors, Thromboxane / Q000032:analysis*; D013931:Thromboxanes / Q000096:biosynthesis / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C045749:SQ 29548