Distribution of angiotensin II receptor subtypes in rat and human kidney.

Abstract

Angiotensin II initiates a variety of physiological effects in the kidney by binding to high-affinity receptors on plasma membranes. Recently, two subtypes of angiotensin II receptors have been distinguished on the basis of differences in signal transduction mechanisms, binding affinity to agonists and antagonists, and inhibition of binding by dithiothreitol. To evaluate the density and distribution of these receptor subtypes in the kidney, we performed an in situ autoradiographic study on frozen tissue sections obtained from rat and human kidneys. Sections were incubated with 125I-[Sar1,Ile8]angiotensin II and binding specificity was verified by competition with unlabeled [Sar1]angiotensin II. Angiotensin II receptor subtypes were characterized by competition with the nonpeptide receptor antagonists, DuP 753 (type 1) and PD123177 (type 2). Both rat and human kidney exhibited a high concentration of angiotensin II receptors in glomeruli and in the longitudinal bands traversing the outer portion of the medulla, corresponding to the medullary vascular bundles. Binding affinity (Kd = 0.6 +/- 0.4 nM), determined in rat kidney, was similar to that reported previously in isolated glomeruli and membrane vesicles prepared from renal tubules. Angiotensin II binding was almost completely inhibited by DuP 753, whereas PD123177 had little effect. Thus the predominant angiotensin II receptor subtype in both rat and human kidney is type 1. The distribution of angiotensin II receptors correlates well with the intrarenal sites at which the peptide has its major physiological effects.