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 AT₂antagonists, 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 µM) 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 µM) 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.