Autoradiographic characterization of angiotensin receptor subtypes in fetal and adult human kidney

To better understand the action of angiotensin II (ANG II) and angiotensin receptor antagonists (ARA) in human kidney, ANG II receptors were characterized by in vitro autoradiography in fetal and adult human renal tissue using 125I-Sar1-Ile8ANG II (125I-ANG II), a potent ANG II antagonist. Binding was inhibited with the ARAs DuP 753 and PD 123177, respectively. In adult kidneys (n = 5), binding of 125I-ANG II showed the following characteristics: arterial vessels had dissociation constant (Kd) = 387.6 +/- 29.1 (SD) pM and maximal binding (Bmax) = 41.4 +/- 3.6 fmol/mg tissue equivalent (TE); glomeruli had Kd = 885.7 +/- 217.1 pM and Bmax = 35.5 +/- 8.1 fmol/mg TE; and outer medulla had Kd = 142.1 +/- 52.5 pM and Bmax = 7.7 +/- 2.3 fmol/mg TE. PD 123177 effectively displaced 125I-ANG II only in large preglomerular vessels half-maximal inhibitory concentration (IC50) = 0.22 +/- 0.1 nM, type 2 receptor (AT2), whereas DuP 753 displaced only the labeled ligand in glomeruli (IC50 = 0.28 +/- 0.11 nM) and outer medulla (IC50 = 0.39 +/- 0.11 nM, AT1). In fetal kidneys (n = 4), a diffuse 125I-ANG II binding was demonstrated in the medulla (Kd = 36.6 +/- 7.1 pM; Bmax = 25 +/- 3.8 fmol/mg TE) and in the cortex (Kd = 19.5 +/- 8 pM; Bmax = 7.2 +/- 2.2 fmol/mg TE). Both cortical (IC50 = 0.039 +/- 0.019 nM) and medullary binding (IC50 = 0.076 +/- 0.039 nM) could only be displaced by PD 123177.(ABSTRACT TRUNCATED AT 250 WORDS)