Characterization of [3H]losartan receptors in isolated rat glomeruli

Eur J Pharmacol. 1993 Oct 15;247(2):193-8. doi: 10.1016/0922-4106(93)90077-m.

Abstract

[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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Biphenyl Compounds / metabolism*
  • Dithiothreitol / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Imidazoles / metabolism*
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Losartan
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Angiotensin / metabolism*
  • Saralasin / metabolism
  • Tetrazoles / metabolism*

Substances

  • Biphenyl Compounds
  • Imidazoles
  • Iodine Radioisotopes
  • Receptors, Angiotensin
  • Tetrazoles
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Saralasin
  • Losartan
  • Dithiothreitol