Characterization of [3H]losartan receptors in isolated rat glomeruli.
[3H]Losartan bound specifically to isolated rat glomeruli. Scatchard analysis revealed a single class of losartan binding sites with an apparent dissociation constant (KD) of 6.2 nM and a density of receptor sites (Bmax) of 1.2 pmol/mg protein. In comparison, [3H][Sar1,Ala8]angiotensin II binding sites exhibited the same KD value (4.3 nM), but a considerably lower Bmax (52 fmol/mg protein). Moreover whereas [125I][Sar1,Ala8]angiotensin II was almost equally displaced by angiotensin II, [Sar1,Ala8] angiotensin II and losartan, [3H]losartan was potently displaced by losartan only. Finally, [125I][Sar1,Ala8]angiotensin II but not [3H]losartan binding sites were sensitive to guanosine triphosphate (GTP) gamma S and Dithiothreitol. These data, together with the recent demonstration of intrinsic effects of losartan, support the view that [3H]losartan does not label only the angiotensin II type 1 receptor (AT1).
Chansel
D
D
INSERM 64, Hôpital Tenon, Paris, France.
Vandermeersch
S
S
Pham
P
P
Ardaillou
R
R
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001713:Biphenyl Compounds / Q000378:metabolism*; D004229:Dithiothreitol / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D019808:Losartan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012504:Saralasin / Q000378:metabolism; D013777:Tetrazoles / Q000378:metabolism*
D001713:Biphenyl Compounds; D007093:Imidazoles; D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012504:Saralasin; D019808:Losartan; D004229:Dithiothreitol