Angiotensin-(1-7) binds at the type 1 angiotensin II receptors in rat renal cortex.
Significant angiotensin (Ang) (1-7) production occurs in kidney and effects on renal function have been observed. The present study was undertaken to investigate binding characteristics of the heptapeptide to Ang II receptors present in rat renal cortex. [125I]-Ang II binding to rat glomeruli membranes was analyzed in the presence of increasing concentrations of Ang II, Ang-(1-7), DUP 753 and PD 123319. Linearity of the Scatchard plot of the [125I]-Ang II specific binding to rat glomeruli membranes indicated a single population of receptors, with a Kd value of 0.7 +/- 0.1 nM and a Bmax of 198 +/- 0.04 fmol/mg protein. DUP 753, an specific AT1 receptor antagonist, totally displaced the specific binding of [125I]-radiolabelled hormone with a Ki of 15.8 +/- 0.9 nM, while no changes were observed in the presence of the selective AT2 receptor antagonist, PD 123319. The specific [125I]-Ang II binding to rat glomerular membranes was displaced by Ang-(1-7) with high affinity (Ki = 8.0 +/- 3.2 nM). We conclude that radioligand binding assays in the presence of selective Ang II antagonists DUP 753 and PD 123319 suggest the unique presence of AT1, receptors in rat glomeruli and a possible role in the control of the biological renal effects of Ang-(1-7).
Gironacci
M M
MM
Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Coba
M P
MP
Peña
C
C
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001665:Binding Sites; D007093:Imidazoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007672:Kidney Cortex / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011725:Pyridines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan