Endothelin-1 and -3 binding to ETB receptors in rat renal tubules.
To increase understanding of endothelin (ET) function in the kidney, we investigated binding of the radioligand of endothelin isopeptides to microdissected rat nephron segments. Specific ET-1 binding was highest in the inner medullary collecting duct, whereas the cortical and outer medullary collecting ducts showed moderate binding, as did the glomeruli. There was slight ET-1 binding to the early portion of the proximal tubule. Other nephron segments displayed little ET-1 binding. The binding profile of ET-3 along the nephron markedly resembled that of ET-1. Scatchard analyses of ET-1 and ET-3 binding to cortical collecting ducts revealed a single class of receptor for both ET-1 and ET-3. Displacement of [125I]-ET-1 binding by unlabeled ET-3 was similar to that produced by unlabeled ET-1. Moreover, a specific ETB agonist, BQ-3020, almost completely inhibited [125I]-ET-1 binding in cortical collecting ducts, whereas a specific ETA antagonist, BQ-123, had little effect. These data indicate that cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind equally.
Uchida
S
S
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Takemoto
F
F
Ogata
E
E
Kurokawa
K
K
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C075771:BQ 3020; C072247:cyclo(Trp-Asp-Pro-Val-Leu)