AUTORADIOGRAPHIC CHARACTERIZATION OF ANGIOTENSIN RECEPTOR SUBTYPES IN FETAL AND ADULT HUMAN KIDNEY

被引:112
作者
GRONE, HJ [1 ]
SIMON, M [1 ]
FUCHS, E [1 ]
机构
[1] GERMAN PRIMATE CTR,W-3400 GOTTINGEN,GERMANY
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1992年 / 262卷 / 02期
关键词
ANGIOTENSIN RECEPTORS; ANGIOTENSIN RECEPTOR ANTAGONIST; RENAL GROWTH;
D O I
10.1152/ajprenal.1992.262.2.F326
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 I-125-[Sar1-Ile8]ANG II (I-125-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 I-125-ANG II showed the following characteristics: arterial vessels had dissociation constant (K(d)) = 387.6 +/- 29.1 (SD) pM and maximal binding (B(max)) = 41.4 +/- 3.6 fmol/mg tissue equivalent (TE); glomeruli had K(d) = 885.7 +/- 217.1 pM and B(max) = 35.5 +/- 8.1 fmol/mg TE; and outer medulla had K(d) = 142.1 +/- 52.5 pM and B(max) = 7.7 +/- 2.3 fmol/mg TE. PD 123177 effectively displaced I-125-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 I-125-ANG II binding was demonstrated in the medulla (K(d) = 36.6 +/- 7.1 pM; B(max) = 25 +/- 3.8 fmol/mg TE) and in the cortex (K(d) = 19.5 +/- 8 pM; B(max) = 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. Because human kidneys have two subtypes of ANG II receptors, the renal functional effects of ARA may differ with regard to their binding to one or both of the ANG II receptor subtypes. The high-affinity binding of ANG II to fetal human kidney may be important for renal development.
引用
收藏
页码:F326 / F331
页数:6
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