A new generation of bradykinin antagonists.
Bradykinin B2 receptors are constitutively expressed, and require the entire peptide chain of bradykinin for recognition. Expression of B1 receptors is induced in inflammation; they recognize BK-(1-8). Heretofore blockade of all the actions of bradykinin required two different antagonists, one for each class of receptors. The new antagonists described here are full chain antagonists having high potency on B2 receptors, but they are also very potent antagonists for B1 receptors. They are highly resistant to kininases and show very long action in vivo. These antagonists contain the novel amino acid alpha-(2-indanyl)glycine (IgI) at positions 5 and 7. The peptide DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg (designated B9430) shows all these desirable characteristics. It represents a new class of bradykinin antagonist peptides.
Stewart
J M
JM
Department of Biochemistry, University of Colorado School of Medicine, Denver 80262, USA.
Gera
L
L
Hanson
W
W
Zuzack
J S
JS
Burkard
M
M
McCullough
R
R
Whalley
E T
ET
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D065168:Bradykinin Receptor Antagonists; D004285:Dogs; D004355:Drug Stability; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D014599:Uterus / Q000187:drug effects / Q000502:physiology
D065168:Bradykinin Receptor Antagonists; D009842:Oligopeptides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D001920:Bradykinin