In vitro Autoradiography Reveals Predominantly AT1 Angiotensin II Receptors in Rat Kidney
Kidney and Blood Pressure Research, 1992•karger.com
Abstract 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 n
M) and proximal tubules (Ki= 43.4±17 n M). By contrast, the AT2 antagonists, PD 123177
and CGP 42112A, were very weak in competing for specific 125I-[Sar1, Ile8] Ang II binding …
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 n
M) and proximal tubules (Ki= 43.4±17 n M). By contrast, the AT2 antagonists, PD 123177
and CGP 42112A, were very weak in competing for specific 125I-[Sar1, Ile8] Ang II binding …
Abstract
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 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.
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