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Evidence for renal glomerular receptors for angiotensin II

1974; Elsevier BV; Volume: 6; Issue: 4 Linguagem: Inglês

10.1038/ki.1974.105

1523-1755

Jean Daniel Sraer, Josée Sraer, Raymond Ardaillou, Odile Mimoune,

Receptor Mechanisms and Signaling

Evidence for renal glomerular receptors for angiotensin II. Monoiodinated angiotensin II (2000 mCi/μmole) was found to bind specifically to isolated rat glomeruli. Equilibrium was reached after 12 min and specific binding represented more than 95% of total binding. Dissociation after addition of an excess of unlabelled molecules was rapid. The k 1 and k -1 association and dissociation constants determined from time-course studies were 0.254±0.078 × 10 10 M -1 min -1 and 0.102±0.018 min -1 , respectively and the ratio k -1 /k 1 (K D ) was 4.51±0.55 × 10 -11 M. Angiotensin II, liberated from glomerular binding sites at low pH, retained the ability to bind to fresh membranes. Angiotensin II, angiotensin I, ileu 8 -angiotensin II and sarc 1 -ileu 8 -angiotensin II were all equally effective as competitive inhibitors of 125 I-angiotensin binding. In a preparation of isolated rat glomeruli, mean glomerular diameter decreased as a function of 125 I-angiotensin II concentration according to a sigmoidal effect vs. log dose curve and the calculated K D (6 × 10 -11 M) was similar to that obtained from binding studies. Specific binding of angiotensin II at physiological plasma concentration to rat glomeruli and correlation of this binding with glomerular vasoreactivity suggest a physiological role for this hormone in regulation of glomerular filtration. Recepteurs renaux glomerulaires de l'angiotensine II. L'Angiotensine II monoiodee (2000 mCi/μmole) se lie specifiquement aux glomerules de rat isoles. L'equilibre est atteint au bout de 12 mn et la fixation specifique represente plus de 95% de la fixation totale. L'addition d'un exces d'angiotensine non marquee determine une dissociation rapide de l'hormone fixee. Les constantes d'association (k 1 ) et de dissociation (k -1 ) calculees a partir des experiences de fixation en fonction du temps sont egales a 0,254±0,078 × 10 10 M -1 mn -1 et 0,102±0,018 mn -1 , respectivement. Le rapport k -1 / k1 (K D ) est egal a 4,51 ±0,55 × 10 -11 M. L'angiotensine II, eluee a pH acide de ses sites glomerulaires de liaison, garde la capacite de se lier de nouveau a des membranes fraiches. L'angiotensine II, l'angiotensine I, la ileu 8 -angiotensine II et la sarc 1 -ileu 8 -angiotensine II sont des inhibiteurs competitifs de la 125 I-angiotensine II, tous de meme efficacite. Le diametre glomerulaire moyen mesure dans une preparation de glomerules isoles decroit en fonction de la concentration de la 125 I-angiotensine II selon une courbe sigmoide (effet contre le log de la dose) et le K D calcule (6 × 10 -11 M) est semblable a celui obtenu a partir des experiences de liaison. La fixation specifique aux glomerules de rat de l'angiotensine II a des concentrations identiques a celles presentes physiologiquement dans le plasma, ainsi que la correlation entre la liaison de l'hormone aux glomerules et la vasomotricite glomerulaire suggerent un role physiologique de l'angiotensine II dans la filtration glomerulaire.