Inhibition of 3H-Angiotensin II binding to zona glomerulosa cells by several analogs

Inhibition of 3H-angiotensin II (Ang II) binding to zona glomerulosa cells prepared from male rabbit adrenals, was determined by addition of approximately equimolar (10(-8)) concentrations of unlabelled peptide analogs. The unlabelled octapeptide inhibited binding by 20%, while the heptapeptide analog [des-Asp1, Ile8] Ang II inhibited by 51%. Octapeptide analogs with sarcosine substituted in position one all inhibited more than 50% of the bound ligand ([Sar1, Ala8] Ang II, 55%; [Sar1, Thr8] Ang II, 58%; [Sar1, Ile8] Ang II, 68%, and [Sar1] Ang II, 62%). Addition of other octapeptide analogs ([Ile8] Ang II, [Ala(betathi)] Ang II, [MeAla1, Ile8] Ang II, and [Me2Gly1] Ang II) inhibited 30-40% of the labelled hormone. [Ser(OAc)]n - [Asp1, Ile5] Ang II at two different concentrations inhibited less than 10%. Increasing concentrations (10(-9)M-10(-7)M) of the analogs produced increased inhibition of angiotensin binding to zona glomerulosa cells. These results seem to correlate well with reports that show sarcosine substituted analogs to be the best antagonists of angiotensin-induced aldosterone biosynthesis or release.