Comparative effects of angiotensin II and angiotensin III in rabbit adrenal and aortic tissues.
The addition of angiotensin II (AII) and angiotensin III (AIII) to isolated tissue baths produced the same maximal contractile response of rabbit aortic strips. AIII was about 10 times less potent, the slope of its concentration-response curve was less steep and its rate of onset slower than that of AII. The responses of both AII and AIII were inhibited with equal potency by the surmountable AII antagonist Phe4, Tyr8-AII and its unsurmountable analog Sar1, Leu8-AII but the kinetic patterns of inhibition by both were less well defined with the agonist AIII than with AII. The addition of AIII to tissues which had exhibited a maximal response to AII did not increase the level of contraction, in contrast to the case when norepinephrine was added to tissues contracted by AII. Both AII and AIII displaced [125I]AII binding from rabbit adrenal membranes; AIII was 6 times less potent than AII but displayed competitive kinetics as an inhibitor of [125I]AII binding. In further studies two binding sites for [125I]AII were identified in adrenal membranes, having KD values of 2.0 +/- 0.2 and 19.6 +/- 2.3 nM, respectively. Each site was inhibited by both AII and AIII and the ratio of the apparent Ki values for the two hormones was not significantly different. The Hill coefficient for the high affinity site was, however, lower for AIII than AII. We interpret our data to suggest that AII and AIII act on the same receptors. AIII apparently binds less efficiently than does AII in both rabbit adrenal membranes and rabbit aortic strips.
Pendleton
R G
RG
Rhône-Poulenc Rorer Central Research, King of Prussia, Pennsylvania.
Gessner
G
G
Horner
E
E
D000311:Adrenal Glands / Q000187:drug effects*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000805:Angiotensin III / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000032:analysis*; D014661:Vasoconstriction / Q000187:drug effects
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III