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 B_max values in the liver obtained from saturation isotherms using [³H]losartan (B_max = 194 pmol g tissue) and [¹²⁵I]sarcosine¹,isoleucine⁸ angiotensin II (B_max = 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 μM 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.