Characterization of putative glomerular receptors for angiotensin II in the rainbow trout Oncorhynchus mykiss using the antagonists Losartan, PD 123177, and saralasin.
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.
Cobb
C S
CS
Department of Biological Sciences, Hatherly Laboratories, University of Exeter, UK.
Brown
J A
JA
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*
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