CHARACTERIZATION OF BRAIN ANGIOTENSIN-II AT2-RECEPTOR SUBTYPE USING [I-125] CGP-42112A

RECENTLY two subtypes of angiotensin receptors have been described, AT1 and AT2. Currently used radiolabeled agonists and antagonists are not able to discriminate between these receptor subtypes. Here we characterize the use of [I-125] CGP 42112A, a novel, specific ligand for AT2 receptors, in a membrane binding assay and in autoradiography of brain sections of 2 week old rats. [I-125] CGP 42112A bound with high affinity and autoradiography revealed binding selectively localized to areas known to express the AT2 receptor subtype only. CGP 42112A, angiotensin II, angiotensin Ill and PD 123177 competed for [I-125] CGP 42112A binding, with potencies consistent with high affinity and specific binding to AT2 receptors. Thus [I-125] CGP 42112A will be a useful new tool to study AT2 receptors.