Premium
Comparative pharmacology of recombinant rat AT 1A , AT 1B and human AT 1 receptors expressed by transfected COS‐M6 cells
Author(s) -
Balmforth Anthony J.,
Bryson Susan E.,
Alison J. Aylett,
Warburton Philip,
Ball Stephen G.,
Pun KwokTao,
Middlemiss David,
Drew G. Michael
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13064.x
Subject(s) - receptor , losartan , angiotensin ii , radioligand assay , radioligand , angiotensin receptor , transfection , recombinant dna , biology , antagonist , chemistry , affinities , biochemistry , pharmacology , stereochemistry , gene
1 Currently available antagonists and agonists cannot distinguish between 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 losartan (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 AT 1 receptor subtypes, we determined whether any of these compounds could 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 [ 125 I]‐Sar 1 Ile 8 angiotensin II for binding to the AT 1 receptors. 4 Direct comparisons of the pIC 50 values of individual compounds for rat AT 1A , AT 1B and human AT 1 receptors revealed only minor differences. 5 It is concluded that compounds based structurally on losartan are unlikely to distinguish between these receptors.