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

The effects of the angiotensin-II (AII) 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 AII 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 AII 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 AII agonists in inhibiting 125I-SARILE binding was AII >> AIII = AI. The difference in rank order of potency between the functional and binding assay 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.