Uta Wethmar, Walter Raasch, Andreas Dendorfer and Peter Dominiak*
Institute of Experimental and Clinical Pharmacology and Toxicology, Medical
University of L歹ck, Ratzeburger Allee 160, 23538 L歹ck, Germany
*Corresponding author. FAX: +49-451-5003327
E-mail: dominiak@medinf.mu-luebeck.de
Abstract: 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 mM failed to displace
the specific binding of [125I]Sar 1,Ile8
angiotensin II at the AT1-receptor characterized by losartan
(IC50 =26ｱ12 nM) in liver homogenate. The same substances up
to 100 mM produced no reduction of specific [125I]Sar1,Ile8
angiotensin II binding to the AT2-receptor of phaeochromocytoma
cell membranes characterized by PD123319 (IC50=20ｱ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ｱ13 nM) and the
I2-ligand idazoxan (IC50=3.29ｱ0.88 mM).
The investigated AT-receptor ligands angiotensin II, losartan, EXP 3174
and PD123319 revealed no displacement of [3H]clonidine up to
a concentration of 100 mM. The I2-receptor
in liver homogenate was characterized by displacement of [3H]idazoxan
by cold idazoxan and clonidine (IC50=0.37ｱ0.17 and 68ｱ31 mM,
respectively). The investigated AT-receptor ligands angiotensin II, losartan
and PD123319 failed to displace [3H]idazoxan specifically up
to 100 mM. Hence, the tested substances showed
no cross-reactivity at the corresponding AT- and I-receptors up to 100 mM,
a concentration markedly higher than the plasma concentrations achieved
after therapeutic application.
Keywords: Angiotensin II-receptor, Imidazoline receptor, AT1-
and AT2-antagonists, Clonidine, Losartan
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