Angiotensin II Receptors in Human Isolated Renal Glomeruli*

125I-Labeled angiotensin II (125IA II) binds specifically to glomeruli isolated from human kidneys that were obtained at nephrectomy or early autopsy. Equilibrium was reached after 30 min, and specific binding represented more than 90% of the total binding. Dissociation after dilution with the addition of an excess of unlabeled hormone was more rapid than after dilution alone. The effect increased as a function of the A II concentration. The Scatchard plot derived from saturation experiments was curvilinear, with an upward concavity. Two groups of receptor sites could be defined by the Kd values (0.1 and 2 nM, respectively) and the number of receptor sites (40 and 300 fmol mg glomerular protein-1, respectively). Alternatively, binding could be considered to follow a negative cooperative type of hormone-receptor interaction. Asn1, Val5A II, Asp1,Ile5A II, des, Asp1,Ile5A II, Sar1, Ala8A II, and Sar1, Ile8A II were all equally effective as competitive inhibitors of 125IA II binding. Both calcium and magnesium (0.5-5 mM) produced an increase in 125IA II specific binding, whereas guanylylimidodiphosphate, an analog of GTP, inhibited it. Degradation of the 125IA II present in the incubation medium was estimated by three different techniques. It increased linearly with time and reached 20% at 30 min. Specific binding of A II to human glomeruli at plasma concentrations observed in man under physiological conditions and during the iv administration of A II demonstrates that human renal glomeruli include target cells for A II and thus suggests a role for A II in regulation of the glomerular filtration rate in man.