Home Life Sciences A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction
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A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction

  • Sheila Siqueira Andrade , Soraya Soubhi Smaili , Priscila Totarelli Monteforte , Antônio Miranda , Maria Kouyoumdjian , Misako Uemura Sampaio , Guiomar Silva Lopes and Maria Luiza V. Oliva EMAIL logo
Published/Copyright: September 1, 2012
Biological Chemistry
From the journal Biological Chemistry Volume 393 Issue 9

Abstract:

BbKI is a kallikrein inhibitor with a reactive site sequence similar to that of kinins, the vasoactive peptides inserted in kininogen moieties. This structural similarity probably contributes to the strong interaction with plasma kallikrein, the enzyme that releases, from high-molecular weight kininogen (HMWK), the proinflammatory peptide bradykinin, which acts on B2 receptors (B2R). BbKI was examined on smooth muscle contraction and Ca2+ mobilization, in which the kallikrein-kinin system is involved. Contrary to expectations, BbKI (1.8 μm) increased [Ca2+]cand contraction, as observed with BK (2.0 μm). Not blocked by B1 receptors (B1R), the BbKI agonistic effect was blocked by the B2R antagonist, HOE-140 (6 μm), and the involvement of B2R was confirmed in B2R-knockout mice intestine. The same tissue response was obtained using a synthetic peptide derived from the BbKI reactive site structure, more resistant than BK to angiotensin I-converting enzyme (ACE) hydrolysis. Depending on the concentration, BbKI has a dual effect. At a low concentration, BbKI acts as a potent kallikrein inhibitor; however, due to the similarity to BK, in high concentrations, BbKI greatly increases Ca2+ release from internal storages, as a consequence of its interaction with B2R. Therefore, the antagonistic and agonistic effects of BbKI may be considered in conditions of B2R involvement.

Keywords: B2 receptor; bradykinin; calcium; Kunitz inhibitor; smooth muscle; trypsin inhibitor
Corresponding author: Maria Luiza V. Oliva, Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio 100, 04044-020 São Paulo, SP, Brazil
Received: 2012-2-22
Accepted: 2012-7-2
Published Online: 2012-09-01
Published in Print: 2012-09-01

©2012 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/hsz-2012-0126
Keywords for this article
B2 receptor; bradykinin; calcium; Kunitz inhibitor; smooth muscle; trypsin inhibitor

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Guest Editorial
  4. Highlight: The universe of proteolytic networks and mechanisms
  5. Highlight: 7th General Meeting of the International Proteolysis Society
  6. Current and prospective applications of non-proteinogenic amino acids in profiling of proteases substrate specificity
  7. Understanding the substrate specificity of conventional calpains
  8. Protease-dependent mechanisms of complement evasion by bacterial pathogens
  9. An ensemble view of thrombin allostery
  10. Processive proteolysis by γ-secretase and the mechanism of Alzheimer’s disease
  11. TMPRSS4 is a type II transmembrane serine protease involved in cancer and viral infections
  12. A catalogue of putative HIV-1 protease host cell substrates
  13. 10.1515/hsz-2012-0162
  14. 10.1515/hsz-2012-0126
  15. Characterisation and metabolism of astroglia-rich primary cultures from cathepsin K-deficient mice
  16. 10.1515/hsz-2012-0175
  17. Review
  18. Synthesis and biological actions of diphosphoinositol phosphates (inositol pyrophosphates), regulators of cell homeostasis
  19. Minireviews
  20. Redox Biology on the rise
  21. Adipose triglyceride lipase in immune response, inflammation, and atherosclerosis
  22. Research Articles/Short Communications
  23. Protein Structure and Function
  24. 10.1515/hsz-2012-0183
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