Kinins IV pp 537-542 | Cite as

Bradykinin Competitive Antagonists for Classical Kinin Systems

  • John M. Stewart
  • Raymond J. Vavrek
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)


The substitution of D-phenylalanine for proline at position 7 of bradykinin (BK) converts BK into a specific antagonist. Additional modifications of the nonapeptide structure, especially the inclusion of β-2-thienylalanine residues (Thi) for phenylalanine at positions 5 and 8, increase antagonist potency in the classic smooth muscle (isolated rat uterus and guinea pig ileum) and rat blood pressure kinin assays. [ Thi5,8,DPhe7]-BK had a pA2 value of 6.5 for inhibition of the BK response on rat uterus, and 6.3 on guinea pig ileum. Addition of Lys-Lys- or a D-Arg- residue to the N-terminal of D-Phe7-substituted antagonists decreases uterine agonist activity, but does not affect inhibitory potency on the ileum. Addition of a D-proline residue in place of proline in position 3 of D-Arg- extended antagonists produces specific uterine inhibitors which show no antagonism on the ileum. The D-Phe7-analogs did not inhibit smooth muscle responses to substance-P or angiotensin-II, and the antagonism of kinin responses was competitive.


Agonist Potency Amino Isobutyric Acid Smooth Muscle Response Ileum Preparation Bradykinin Analog 
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  1. 1.
    E. Schroeder, Structure-activity relationships of kinins, in; Handbook of Experimental Pharmacology, Vol. XXV, ed. by E. G. Erdos, Springer-Verlag, pp. 324–350, (1970),Google Scholar
  2. 2.
    J. M. Stewart, Chemistry and biologic activity of peptides related to bradykinin, in: Handbook of Experimental Pharmacology, Vol. XXV Supplement, ed. by E. G. Erdos, Springer-Verlag, pp. 227–272, (1979).Google Scholar
  3. 3.
    A. Geese, E. Zsilinszky, and L. Szekeres, Bradykinin antagonism, Adv. Exptl. Med. Biol., 70: 5–13, (1976).Google Scholar
  4. 4.
    G. Claeson, J. Fareed, C. Larsson, G. Kindel, S. Arielly, R. Simonsson, H. L. Messmole, and J. U. Balis, Inhibition of the contractile action of bradykinin on isolated smooth muscle preparations by derivatives of low molecular weight peptides, Adv. Exptl. Biol. Med., 120B: 691–713, (1979).Google Scholar
  5. 5.
    R. J. Vavrek and J. M. Stewart, Bradykinin analogs containing a-aminoisobutyric acid (Aib), Peptides, 1: 231–235, (1980).PubMedCrossRefGoogle Scholar
  6. 6.
    J. Roblero, J. W. Ryan, and J. M. Stewart, Assay of kinins by their effects on blood pressure, Res. Commun. Pathol. Pharmacol., 6: 207–212, (1973).Google Scholar
  7. 7.
    H. O. Schild, pA, a new scale for the measurement of drug antagonism, Br. J. Pharmacol., 2: 189, (1947).Google Scholar
  8. 8.
    F. W. Dunn and J. M. Stewart, Analogs of bradykinin containing 6-2- thienyl-L-alanine, J. Med. Chem., 14: 779–781, (1971).PubMedCrossRefGoogle Scholar
  9. 9.
    C. E. Odya, T. L. Goodfriend, and C. Pena, Bradykinin receptor-like binding studied with iodinated analogs, Biochem. Pharmacol., 29: 175–185, (1980).Google Scholar
  10. 10.
    E. Schroeder, Synthese und biologische aktivitat bradykininwirksamer undeca-, dodeca- und tridecapeptide, Experientia, 21: 271–276, (1965).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • John M. Stewart
    • 1
  • Raymond J. Vavrek
    • 1
  1. 1.Department of BiochemistryUniversity of Colorado School of MedicineDenverUSA

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