Comparison of the Binding and Functional Actions of Angiotensin Agonists in Clone 9 Cells: Additional Evidence for Angiotensin II Receptor Heterogeneity

Abstract

The effects of the angiotensin-II (All) agonists and antagonists on both ¹²⁵I-SARILE binding and phosphoinositol (PI) accumulation in clone 9 cells were examined. Clone 9 cells, which are derived from rat liver, have been shown to respond to All agonists with an increase in PI accumulation which is inhibitable by Sar₁, Ile₈-AII (SARILE) and DUP-753 but not PD-123319, suggesting that they possess the AT₁ subtype of All receptor. The present results confirmed these properties. The order of potency of AII agonists was AII> AIII> AI. Clone 9 cells also possessed binding sites for ¹²⁵I-SARILE. The majority of these were AT₁ type receptors, although a small number of AT₂ receptors may also have been present. The order of potency of All agonists in inhibiting ¹²⁵-SARILE binding was All » AIII> = AI. The difference in rank order of potency between the functional and binding assays was due to AIII being much less potent in the binding assay than the functional assay. Since the potency of AIII relative to AII was lower than that at either AT₁ or AT₂ subtypes of AII receptor, these data suggest that an additional subtype, with selectively low affinity for AIII, exists.