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 M) 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 M) of the AT1 antagonist, DuP 753, represent approximately 5% of total 0renal 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.