Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney

摘要: Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ET A B in human kidney. Endothelins (ET), a group of vasoconstrictor peptides, are expressed wide range tissues species bind to specific receptors which there at least two subtypes, . The kidney has been found animal studies be highly sensitive the effects ET. We have used new peptide ligands, selective for particular (the antagonist agonist ) binding renal receptors. Saturation gave equilibrium dissociation constants (K d [I 125 ]ET-1 0.17 ± 0.04 nM ]BQ3020 0.36 0.06 nM. Hill coefficients were 0.86 0.03 0.77 0.04, respectively. Macro- microautoradiography using ]-labeled with as competing blockers showed majority medulla concentration vasa recta bundles, localizing vascular smooth muscle. subtype predominated over by about 2:1, was more generally distributed, collecting system. These findings confirmed competition assays giving max values (ET /ET , fmol/mg protein), cortex, respectively, 18.7 2.2/11.3 2.7 12.7 3.9/7.6 3.5 BQ3020; 36.2 5.6/11.1 4.1 14.9 1.6/5.3 0.2 BQ123. This study establishes distribution demonstrates that novel thousand-fold selectivities - -receptor results show that, contrast other such heart, contains predominantly subtype.