Binding and pharmacologic properties of peptides derived from human and rat angiotensin II (AII) mRNA.
We investigated the binding and pharmacologic properties of peptides encoded by complementary mRNA derived from the human and rat angiotensinogen gene (human and rat IIA, respectively). Human IIA (identical with AII in 4 amino acids) inhibited binding of [125I]AII to rat adrenal glomerulosa particles (Ki = 0.62 +/- 0.09 microM) and competitively blocked, with similar potency, the ability of three AII receptor agonists to contract rabbit aorta. Rat IIA affected neither [125I]AII binding to glomerulosa particles nor the contractile response of AII. We conclude that rat IIA does not interact with AII or its receptors and that human IIA acts as a competitive inhibitor of AII at the receptor level.
Wiest
S A
SA
Department of Cardiovascular Pharmacology, Lilly Research Laboratories, Indianapolis, Indiana.
Gesellchen
P D
PD
Zimmerman
K
K
Steinberg
M I
MI
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics*; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000235:genetics* / Q000378:metabolism; D000808:Angiotensinogen / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001483:Base Sequence; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II