Angiotensin II and non-angiotensin II displaceable binding sites for [3H]losartan in the rat liver.
By virtue of the more than 1000-fold selectivity of losartan (DuP 753) for the AT1 angiotensin II (AII) receptor subtype compared with the AT2 subtype, [3H]losartan may be a useful radioligand for studies of the AT1 receptor subtype. Comparison of Bmax values in the liver obtained from saturation isotherms using [3H]losartan (Bmax = 194 pmol/g tissue) and [125I]sarcosine1,isoleucine8 angiotensin II (Bmax = 20 pmol/g tissue) indicated that the AII receptor concentration was approximately 10% that of the [3H]losartan binding sites. In addition, AII at concentrations as high as 10 microM displaced less than one-third of specific [3H]losartan binding in the liver and less than 80% in the whole adrenal. The presence of non-AII displaceable [3H]losartan binding in the liver did not appear to result from metabolism of the radioligand since HPLC analysis of free and bound 3H revealed that greater than 90% of the 3H eluted at the same time as the parent [3H]losartan. This suggests that [3H]losartan binds with high affinity to a site(s) other than angiotensin II receptors in the rat liver.
Grove
K L
KL
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520.
Speth
R C
RC
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D019808:Losartan; D008297:Male; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism; D013777:Tetrazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014316:Tritium
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014316:Tritium; D000804:Angiotensin II; C070967:L 158809; D019808:Losartan