ANGIOTENSIN-II AND NON-ANGIOTENSIN-II DISPLACEABLE BINDING-SITES FOR [H-3] 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 A T2 subtype, [H-3]losartan may be a useful radioligand for studies of t he AT1 receptor subtype. Comparison of B(max) values in the liver obta ined from saturation isotherms using [H-3]losartan (B(max) = 194 pmol/ g tissue) and [I-125]sarcosine1,isoleucine8 angiotensin II (B(max) = 2 0 pmol/g tissue) indicated that the AII receptor concentration was app roximately 10% that of the [H-3]losartan binding sites. In addition, A II at concentrations as high as 10 muM displaced less than one-third o f specific [H-3]losartan binding in the liver and less than 80% in the whole adrenal. The presence of non-AII displaceable [H-3]losartan bin ding in the liver did not appear to result from metabolism of the radi oligand since HPLC analysis of free and bound H-3 revealed that greate r than 90% of the H-3 eluted at the same time as the parent [H-3]losar tan. This suggests that [H-3]losartan binds with high affinity to a si te(s) other than angiotensin II receptors in the rat liver.