Comparative studies of receptor binding and steroidogenic properties of angiotensins in the rat adrenal glomerulosa.
Angiotensin and analogs were tested in isolated rat adrenal zona glomerulosa cells to find if there was a correlation between receptor affinity and steroidogenic potency. Comparative receptor-binding affinities and corresponding aldosterone-releasing effects obtained for each analog were: [Asp1, Ile5]angiotensin II, 1.0 and 1.0: [Asp1, Val5]angiotensin II, 0.69 and 1.65; [Asn1, Val5]angiotensin II, 1.18 and 0.68; [Sar1]angiotensin II, 2.07 and 1.7; [Me2Gly1]angiotensin II, 0.63 and 0.72; [Ile5]angiotensin III, 0.72 and 0.59; [Val5]angiotensin III, 0.92 and 0.34; [Ile5]angiotensin I, 0.007 and 0.051; des-Asp1-[Ile5]-angiotensin I, 0.004 and 0.03; and [Val5, Ser9]angiotensin I, 0.03 and 0.098. Taken as a group, these agonist analogs demonstrated good correlations between these two variables (r = 0.76; P less than 0.001). There was parallelism between binding inhibition and aldosterone-releasing effect when position 5 was substituted with isoleucine, regardless of the substituent in position 1 of the angiotensins. This parallelism was lost when analogs of angiotensin II or III contained valine in position 5. In addition, angiotensin III was found to be less potent than angiotensin II, regardless of the substituent in position 5 (valine or isoleucine).
D000450:Aldosterone / Q000096:biosynthesis*; D000809:Angiotensins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000809:Angiotensins; D011955:Receptors, Drug; D000450:Aldosterone