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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)

Summary

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.

Keywords

Agonist Potency Amino Isobutyric Acid Smooth Muscle Response Ileum Preparation Bradykinin Analog 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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