Interactions of ligands at angiotensin II-receptors and imidazoline receptors

Ligands for angiotensin II-(AT)-receptors and imidazoline receptors have st ructural similarities and influence blood pressure via various mechanisms. The goal of this study was to study the specificity of various ligands by d isplacement experiments. Antazoline, cimetidine, clonidine, efaroxan, guana benz, guanethidine, idazoxan, moxonidine and rilmenidine up to a concentrat ion of 100 muM failed to displace the specific binding of [I-125]Sar(1),Ile (8) angiotensin II at the AT(1)-receptor characterized by losartan (IC50 = 26 +/- 12 nM) in liver homogenate. The same substances up to 100 muM produc ed no reduction of specific [I-125]Sar(1),Ile(8) angiotensin II binding to the AT(2)-receptor of phaeochromocytoma cell membranes characterized by PD1 23319 (IC50 = 20 +/- 5 nM). Displacement experiments at the imidazoline I-1 -receptors were performed on bovine adrenal medulla membranes using [H-3]cl onidine after characterization by the II-ligand clonidine (IC50 = 459 +/- 1 3 nM) and the I-2-ligand idazoxan (IC50 = 3.29 +/- 0.88 muM). The investiga ted AT-receptor ligands angiotensin II, losartan, EXP 3174 and PD123319 rev ealed no displacement of [H-3]clonidine up to a concentration of 100 muM. T he It-receptor in liver homogenate was characterized by displacement of [H- 3]idazoxan by cold idazoxan and clonidine (IC50 = 0.37 +/- 0.17 and 68 +/- 31 muM, respectively). The investigated AT-receptor ligands angiotensin II, losartan and PD123319 failed to displace [H-3]idazoxan specifically up to 100 muM. Hence, the tested substances showed no cross-reactivity at the cor responding AT- and I-receptors up to 100 muM, a concentration markedly high er than the plasma concentrations achieved after therapeutic application.