CHARACTERIZATION OF [H-3] LOSARTAN RECEPTORS IN ISOLATED RAT GLOMERULI

[H-3]Losartan bound specifically to isolated rat glomeruli. Scatchard analysis revealed a single class of losartan binding sites with an apparent dissociation constant (K(D)) of 6.2 nM and a density of receptor sites (B(max)) of 1.2 pmol/mg protein. In comparison, [H-3][Sar1,Ala8]angiotensin II binding sites exhibited the same K(D) value (4.3 nM), but a considerably lower B(max) (52 fmol/mg protein). Moreover whereas [I-125][Sar1,Ala8]angiotensin II was almost equally displaced by angiotensin II, [Sar1,Ala8] angiotensin II and losartan, [H-3]losartan was potently displaced by losartan only. Finally, [I-125][Sar1,Ala8]angiotensin II but not [H-3]losartan binding sites were sensitive to guanosine triphosphate (GTP) gammaS and dithiothreitol. These data, together with the recent demonstration of intrinsic effects of losartan, support the view that [H-3]losartan does not label only the angiotensin II type 1 receptor (AT1).