Thromboxane receptors in human kidney tissues.
Thromboxane (TX) A2 effects in the kidneys include contraction of glomerular mesangial cells and intrarenal vascular tissue. A kidney cDNA encoding a TX receptor expressed in rat renal glomeruli and rat renal arterial smooth muscle cells has been reported. However, TXA2 receptors in human kidneys have not been documented. The purpose of this study was to identify and characterize TXA2 receptors in glomeruli and intrarenal arteries isolated from human kidneys. Normal kidneys, not used for transplant because of technical reasons, were kept at -70 degrees C and used for research purposes. The glomeruli and intrarenal arteries were isolated from renal cortical tissue by a mechanical sieving technique. The equilibrium dissociation constant and receptor number were determined by nonlinear analysis of binding inhibition data. The data were generated in radioreceptor assays using [125I]-BOP, a stable analog of TXA2. The dissociation constants (mean +/- SEM) for binding of I-BOP to human glomeruli and intrarenal arterial membranes were 6.6 +/- 1.1 nM (n = 7) and 20 +/- 6 nM (n = 7), respectively (p < 0.05). The receptor number was 311 +/- 91 fmol/mg protein (n = 7) in glomeruli and 74 +/- 16 fmol/mg protein (n = 7) in intrarenal arterial membranes (p < 0.04). The order of specificity of TXA2 analogs for [125I]-BOP binding sites was similar in glomeruli and in arterial membranes and was I-BOP > or = U46619 > or = pinane TXA2 > or = carbocyclic TXA2 > or = PGH2. These findings provide direct evidence for the presence of specific, high-affinity [125I]-BOP binding sites in human renal glomeruli and extraglomerular vascular tissue. These data also indicate that the human binding sites have higher affinity for the TXA2 agonist I-BOP than for PGH2.
Brown
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School of Nursing, State University of New York at Buffalo, 14214, USA. gbrown@nurse.buffalo.edu
Venuto
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000378:metabolism / Q000494:pharmacology; D000081008:Bicyclic Monoterpenes; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D007672:Kidney Cortex / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000032:analysis* / Q000378:metabolism; D012077:Renal Artery / Q000737:chemistry / Q000378:metabolism; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
D000081008:Bicyclic Monoterpenes; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D007457:Iodine Radioisotopes; D008024:Ligands; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C024587:thromboxane A2, carbocyclic; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D013928:Thromboxane A2; C020465:pinane-thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid