Angiotensin II receptor subtypes and their selective nonpeptide ligands

Two types of angiotensin II (AII) receptor (AII-1 and AII-2) have been identified in rat adrenal cortex by means of two highly specific, but structurally dissimilar, nonpeptide AII receptor antagonists, DuP753 and EXP655, and by the discriminatory effect of dithiothreitol (DTT). Using radioligand-receptor binding techniques, DuP753 was found to be highly specific for AII-1 sites, displaying an inhibitory potency value of 1.2 x 10(-8) M. This type of AII receptor was particularly sensitive to inactivation by DTT. EXP655 possessed no affinity for the AII-1 sites, but was highly selective for the AII-2 sites exhibiting an inhibitory potency value of approx 10(-7). The AII-2 receptors were found resistant to DTT inactivation. A limited survey of the tissue distribution of these receptor subtypes indicates that AII-1 sites are exclusively found in vascular tissues, whereas AII-2 sites are highly enriched in adrenal medulla and brain.