Anti-angiotensin antibodies cross-reactive with nonpeptide angiotensin antagonists as angiotensin receptor model.
Anti-angiotensin II (Ang) antibodies could become important receptor mimicking tools if an antibody with binding properties identical to a particular Ang receptor could be generated. For this purpose, anti-Ang sera from mice were screened for antibodies with structure-affinity relationships similar or identical to a particular Ang receptor. Mice were immunized with BSA-coupled [Sar1]Ang and the sera were screened in ELISA for crossreactivity with the Ang analogues saralasin, L158,809, EXP 3147, DuP 753, DuP 532, PD 123177, PD 123319 and the non-related compounds ACTH, naloxone, and CP 96,345. All sera had at least some cross-reactivity with saralasin and some also with L158,809, a potent non-peptide Ang antagonist, selective for the AT1 site. One serum out of eight recognized most Ang analogues except the AT2 selective PD 123177 and PD 123319. ELISA detection antigens were prepared by two different BSA conjugations: [Sar1]Ang was N-terminally attached and [Sar1,Lys8]Ang was C-terminally attached. Against both detection antigens, the peptide antagonists saralasin and [Sar1,Phe(Br5)8]Ang displaced in a sigmoidal manner the antibodies with an IC50-value of 0.4 mM. L158,809 and EXP 3147 displaced also in a parallel manner, suggesting an apparently homogenous population of binding sites. The selectivity profile of the serum has some resemblance to the AT1 selectivity profile but the observed affinities are too low to suggest AT1 receptor mimicry.
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Canada.
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Dagenais
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Escher
D000324:Adrenocorticotropic Hormone / Q000276:immunology; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000276:immunology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001713:Biphenyl Compounds / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000276:immunology / Q000378:metabolism; D019808:Losartan; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009270:Naloxone / Q000276:immunology; D011725:Pyridines / Q000378:metabolism; D012504:Saralasin / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000276:immunology / Q000378:metabolism; D005466:Fluorocarbons
D000324:Adrenocorticotropic Hormone; D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000906:Antibodies; D001713:Biphenyl Compounds; D007093:Imidazoles; D019808:Losartan; D009270:Naloxone; D011725:Pyridines; D012504:Saralasin; D013777:Tetrazoles; C066253:PD 123177; C069045:DuP 532; D005466:Fluorocarbons; C070967:L 158809; C066892:CP 96345