COMPARATIVE PHARMACOLOGY OF RECOMBINANT RAT AT(1A), AT(1B) AND HUMAN AT(1) RECEPTORS EXPRESSED BY TRANSFECTED COS-M6 CELLS

1 Currently available antagonists and agonists cannot distinguish betw een angiotensin AT(1) receptor subtypes. 2 We synthesized a series of compounds selected on the basis of having the most diverse structural features with respect to iosartan (DuP753), the prototype non-peptide AT(1) receptor antagonist. Using a radioligand-receptor binding assay and membranes prepared from COS-M6 cells transfected with individual A T(1) receptor subtypes, we determined whether any of these compounds c ould distinguish between the receptor subtypes. 3 The diversity of the structural features of this series of compounds was reflected by the wide range of affinities (pIC(50) values) displayed towards competing with I-125-Sar(1)Ile(8) angiotensin II for binding to the AT(1) rece ptors. 4 Direct comparisons of the pIC(50) values of individual compou nds for rat AT(1A), AT(1B) and human AT(1) receptors revealed only min or differences. 5 It is concluded that compounds based structurally on losartan are unlikely to distinguish between these receptors.