title: Characterization of putative glomerular receptors for angiotensin II in the rainbow trout Oncorhynchus mykiss using the antagonists Losartan, PD 123177, and saralasin.
abstract: Isolated glomeruli from the rainbow trout Oncorhynchus mykiss have been examined for the presence of receptors specific for angiotensin II (AII). Specific binding of 125I-Asp1Val5-AII was saturable, plateaued after 20 min, and increased with glomerular protein. Saralasin (Sar1Val5Ala8-AII), a nonselective peptide AII receptor antagonist of AII binding to mammalian tissues, was a poor inhibitor of 125I-Asn1Val5-AII binding to trout glomeruli. However, the nonpeptide antagonist, Losartan (= DuP 753), which is specific for AII subtype AT1 receptors in mammalian tissues, was an effective inhibitor of binding of both 125I-Asp1Val5-AII and 125I-Asn1Val5-AII to trout glomeruli. The IC50 for Losartan inhibition of binding of Asp1Val5-AII was 1.25 +/- 0.07 x 10(-8) M while that for inhibition of binding of Asn1Val5-AII was 2.73 +/- 0.45 x 10(-8) M. Statistical analysis of logistic curve fits confirmed the easier displacement of Asp1Val5-AII than of Asn1Val5-AII. PD 123177, a nonpeptide antagonist specific for AII subtype AT2 receptors in mammalian systems, was ineffective as an antagonist of AII binding to trout glomeruli. These results are consistent with the presence of a specific AII receptor in the trout glomerulus and imply a novel receptor configuration.
authors.affiliation: Department of Biological Sciences, Hatherly Laboratories, University of Exeter, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Cobb
authors.forename: J A
authors.initials: JA
authors.lastname: Brown
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007678:Kidney Glomerulus / Q000378:metabolism*; D007700:Kinetics; D019808:Losartan; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000032:analysis / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D007457:Iodine Radioisotopes; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D012504:Saralasin; D019808:Losartan