Changes in glomerular thromboxane A2 receptor expression and ligand binding following immune injury
| Autor: | Barbara A. Bresnahan, Sheng-Hua Wu, Shelly Dufek, Elias A. Lianos |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Thromboxane Receptor expression Kidney Glomerulus Receptors Thromboxane Renal function Ligands urologic and male genital diseases Rats Sprague-Dawley Thromboxane A2 chemistry.chemical_compound Internal medicine medicine Animals Enzyme Inhibitors Receptor prostaglandin H2 [3]H-SQ 29 548 Benzofurans glomerular filtration rate urogenital system Glomerular basement membrane Glomerulonephritis medicine.disease Rats Disease Models Animal Kinetics Endocrinology medicine.anatomical_structure chemistry glomerular basement membrane Nephrology Furegrelate Rabbits Thromboxane-A Synthase Nephritis glomerulonephritis |
| Zdroj: | Kidney International. 55(1):139-147 |
| ISSN: | 0085-2538 |
| DOI: | 10.1046/j.1523-1755.1999.00227.x |
| Popis: | Changes in glomerular thromboxane A 2 receptor expression and ligand binding following immune injury. Background Thromboxane (Tx) A 2 is a potent vasoconstrictor eicosanoid that attains high levels within nephritic glomeruli and mediates a drop in glomerular filtration rate (GFR). In the course of nephritis, however, GFR recovers despite high intraglomerular TxA 2 levels. We hypothesized that this recovery indicates a reduced responsiveness of the glomerular vasculature to TxA 2 , and explored whether changes in TxA 2 receptor protein expression and receptor-ligand binding are underlying mechanisms. Methods Glomerulonephritis was induced in male Sprague-Dawley rats using an antibody raised in rabbits against rat particulate glomerular basement membrane (GBM). Changes in Tx receptor levels were assessed in protein lysates of glomeruli on days 3 and 7 after a single intravenous injection of the anti-GBM antibody. Ligand-binding studies were performed at the same time points using isolated glomeruli and the TxA 2 receptor ligand [ 3 H]-SQ-29,548. GFR was measured as the clearance of endogenous creatinine. Results There was a marked increase in Tx receptor protein in the lysates of nephritic glomeruli on days 3 and 7. In contrast, binding sites (B max ) of [ 3 H]–SQ-29,548 decreased, indicating that the excess receptor became either inaccessible to its ligand (sequestered) or desensitized. Daily administration of the Tx synthase inhibitor Furegrelate starting prior to injection of anti-GBM antibody prevented the decrease in [ 3 H]–SQ-29,548 binding. Furegrelate treatment starting in an established stage of nephritis had no effect. In these animals, GFR was lower than nephritic controls not treated with Furegrelate. Conclusions These observations indicate that in the course of glomerulonephritis, there is a marked increase in glomerular Tx receptor expression. The enhanced intraglomerular TxA 2 synthesis causes either a sequestration or desensitization of its receptor. As a result, access of unbound TxA 2 to efferent arterioles may become facilitated, and constriction of these arterioles may preserve GFR. |
| Databáze: | OpenAIRE |
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