Home Life Sciences Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
Article
Licensed
Unlicensed Requires Authentication

Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist

  • Martin Savard , Julie Labonté , Céléna Dubuc , Witold Neugebauer , Pedro D’Orléans-Juste and Fernand Gobeil EMAIL logo
Published/Copyright: February 2, 2013
Biological Chemistry
From the journal Biological Chemistry Volume 394 Issue 3

Abstract

We recently identified a novel human B2 receptor (B2R) agonist [Hyp3,Thi5,NChg7,Thi8]-bradykinin (NG291) with greater in vitro and in vivo potency and duration of action than natural bradykinin (BK). Here, we further examined its stability and selectivity toward B2R. The hypotensive, antithrombotic, and profibrinolytic functions of NG291 relative to BK and its analogue ([Hyp3,Thi5,(4-Me)Tyr8(ΨCH2NH)Arg9]-BK) (RMP-7) were also tested. Contraction assays using isolated mouse stomachs (containing kinin B1R, B2R, and kininase I- and II-like activities) showed that NG291 is a more potent contractant than BK and is inhibited by HOE-140 (B2R antagonist) but unaffected by R954 (B1R antagonist), whereas both decreased the potency of BK. In stomach tissues from B2R knockout mice, BK maintained its activity via B1R, whereas NG291 had no contractile effect, indicating that it was selective for B2R. Unlike BK, NG291 was not degraded by rabbit lung ACE. Comparing intravenously administered BK and NG291 revealed that NG291 exhibited more potent and prolonged hypotensive action and greater antithrombotic and profibrinolytic activities. These effects were of comparable magnitude to RMP-7 and were absent in B2R knockout mice. We concluded that NG291 is a novel biostable B2R-selective agonist that may prove suitable for investigating the (pre)clinical cardioprotective efficacy of B2R activation.

Keywords: bioassays; bradykinin analogues; cardiovascular system; metabolism; mouse
Corresponding author: Fernand Gobeil Jr., Faculty of Medicine and Health Sciences, Department of Pharmacology, Institute of Pharmacology, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4
Received: 2012-10-4
Accepted: 2013-1-9
Published Online: 2013-02-02
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: Kinin 2012 in Paris
  5. Highlight: Kinin 2012 in Paris
  6. Plasma kallikrein-kinin system and diabetic retinopathy
  7. Tissue kallikrein, blood pressure regulation, and hypertension: insight from genetic kallikrein deficiency
  8. Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output
  9. Interactions between BdkrB2 and p53 genes in the developing kidney
  10. Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
  11. Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice
  12. Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation
  13. Bifunctional epitope-agonist ligands of the bradykinin B2 receptor
  14. Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor
  15. Review
  16. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
  17. Research Articles/Short Communications
  18. Genes and Nucleic Acids
  19. A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer
  20. Protein Structure and Function
  21. SH3-mediated targeting of Wrch1/RhoU by multiple adaptor proteins
https://doi.org/10.1515/hsz-2012-0295
Keywords for this article
bioassays; bradykinin analogues; cardiovascular system; metabolism; mouse

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: Kinin 2012 in Paris
  5. Highlight: Kinin 2012 in Paris
  6. Plasma kallikrein-kinin system and diabetic retinopathy
  7. Tissue kallikrein, blood pressure regulation, and hypertension: insight from genetic kallikrein deficiency
  8. Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output
  9. Interactions between BdkrB2 and p53 genes in the developing kidney
  10. Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
  11. Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice
  12. Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation
  13. Bifunctional epitope-agonist ligands of the bradykinin B2 receptor
  14. Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor
  15. Review
  16. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
  17. Research Articles/Short Communications
  18. Genes and Nucleic Acids
  19. A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer
  20. Protein Structure and Function
  21. SH3-mediated targeting of Wrch1/RhoU by multiple adaptor proteins
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 15.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/hsz-2012-0295/pdf
Scroll to top button