Abstract
-In rat glomeruli and mesangial cells, the thromboxane A 2 (TxA 2) mimetic, U-46,619, but not 8-iso-prostaglandin F 2α (8-isoPGF 2α), reduced glomerular inulin space and increased inositol 1,4,5-trisphosphate production, effects abolished by SQ29,548. In competitive binding studies using 8-iso-[ 3H]PGF 2α or [ 3H]SQ-29,548, mesangial cells displayed TxA 2 binding sites but not ones for 8-iso-PGF 2α. In contrast, rat aortic smooth muscle cells possessed specific binding sites for both TxA 2 and S-iso-PGF 2α and displayed functional responses to both agonists, such as time- and dose-dependent activation of mitogen-activated protein kinases. In these cells, the mean dissociation constant value for the isoprostane receptor was 31.8 ± 5.7 nM. When human TxA 2 receptor cDNA was expressed in Xenopus oocytes injected with the Ca 2+-specific photoprotein, aequorin, 8-iso-PGF 2α gave much weaker responses than U-46,619. These studies provide the first radio-ligand binding characteristics of the F 2-isoprostane receptor and demonstrate its specific and heterologous cellular localization. These studies support the distinct nature and biological significance of isoprostane receptors and provide a tool for their further molecular characterization.
Original language | English (US) |
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Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 272 |
Issue number | 4 PART 2 |
State | Published - 1997 |
Externally published | Yes |
Keywords
- Binding characteristics
- Mitogen-activated protein kinases
- Signal transduction mechanism
ASJC Scopus subject areas
- Physiology (medical)