A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction
| Autor: | Maria Kouyoumdjian, Sheila Siqueira Andrade, Priscila Totarelli Monteforte, Misako U. Sampaio, Antonio Miranda, Guiomar Silva Lopes, Soraya S. Smaili, Maria Luiza Vilela Oliva |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Receptor Bradykinin B2 Trypsin inhibitor Clinical Biochemistry chemistry.chemical_element Bradykinin Calcium Receptor Bradykinin B1 Biochemistry Mice chemistry.chemical_compound Cytosol Internal medicine Bradykinin B2 Receptor Antagonists medicine Animals Drug Interactions Intestinal Mucosa Rats Wistar Receptor Molecular Biology Plant Proteins Mice Knockout Kininogen Binding Sites Muscle Smooth Kallikrein Smooth muscle contraction Intestines Endocrinology Verapamil chemistry Bauhinia Kallikreins Peptides Muscle Contraction |
| Zdroj: | bchm. 393:943-957 |
| ISSN: | 1437-4315 1431-6730 |
| DOI: | 10.1515/hsz-2012-0126 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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