In vitro autoradiography reveals predominantly AT1 angiotensin II receptors in rat kidney.
Angiotensin II (Ang II) receptor subtypes in the rat kidney were investigated by using type 1 (AT1) and type 2 (AT2) Ang II receptor antagonists to discriminate specific 125I-[Sar1,Ile8] Ang II binding sites with in vitro autoradiography. DuP 753, a nonpeptide Ang II antagonist specific for the AT1 sites, potently displaced binding in glomeruli (Ki = 23.9 +/- 3.3 nM) and proximal tubules (Ki = 43.4 +/- 17 nM). By contrast, the AT2 antagonists, PD 123177 and CGP 42112A, were very weak in competing for specific 125I-[Sar1,Ile8] Ang II binding sites. AT1 receptors, as determined in the presence of an excess concentration (10 microM) of the AT2 antagonist, PD 123177, account for 95% of total renal Ang II receptors, whereas AT2 receptors, as determined in the presence of an excess concentration (10 microM) of the AT1 antagonist, DuP 753, represent approximately 5% of total renal Ang II receptors. In addition, the reducing agent, dithiothreitol, produces a dose-dependent inhibition of Ang II receptor binding with an IC50 of 2 mM, a characteristic of the AT1 receptors. These findings indicate that the AT1 receptor is the predominant subtype at multiple anatomical sites in the rat kidney.
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D007668:Kidney / Q000737:chemistry* / Q000000981:diagnostic imaging; D008297:Male; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000032:analysis* / Q000187:drug effects; D014018:Tissue Distribution
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin