2001 Volume 85 Issue 2 Pages 167-174
Ligands for angiotensin II-(AT)-receptors and imidazoline receptors have structural similarities and influence blood pressure via various mechanisms. The goal of this study was to study the specificity of various ligands by displacement experiments. Antazoline, cimetidine, clonidine, efaroxan, guanabenz, guanethidine, idazoxan, moxonidine and rilmenidine up to a concentration of 100 μM failed to displace the specific binding of [125I]Sar1,Ile8 angiotensin II at the AT1-receptor characterized by losartan (IC50 = 26 ± 12 nM) in liver homogenate. The same substances up to 100 μM produced no reduction of specific [125I]Sar1,Ile8 angiotensin II binding to the AT2-receptor of phaeochromocytoma cell membranes characterized by PD123319 (IC50 = 20 ± 5 nM). Displacement experiments at the imidazoline I1-receptors were performed on bovine adrenal medulla membranes using [3H]clonidine after characterization by the I1-ligand clonidine (IC50 = 459 ± 13 nM) and the I2-ligand idazoxan (IC50 = 3.29 ± 0.88 μM). The investigated AT-receptor ligands angiotensin II, losartan, EXP 3174 and PD123319 revealed no displacement of [3H]clonidine up to a concentration of 100 μM. The I2-receptor in liver homogenate was characterized by displacement of [3H]idazoxan by cold idazoxan and clonidine (IC50 = 0.37 ± 0.17 and 68 ± 31 μM, respectively). The investigated AT-receptor ligands angiotensin II, losartan and PD123319 failed to displace [3H]idazoxan specifically up to 100 μM. Hence, the tested substances showed no cross-reactivity at the corresponding AT- and I-receptors up to 100 μM, a concentration markedly higher than the plasma concentrations achieved after therapeutic application.