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Toxins and Hemostasis pp 13–17Cite as

From the Bothrops Jararaca Bradykinin Potentiating Peptides to Angiotensin Converting Enzyme Inhibitors

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Abstract

When Rocha e Silva received the first samples of synthetic bradykinin from Boissonnas et al. (1960), was found that it was much less potent than “natural” bradykinin made by incubation of plasma with the Bothrops jararaca venom. Erdös and Sloane (1962) demonstrated that the major inactivating enzyme in plasma had the characteristics of pancreatic carboxypeptidase B. This enzyme was a zinc metal-enzyme (Vallee, 1961). This knowledge prompted us to investigate the bradykinin potentiating activity of several metal chelating agents. BAL (dimercaptopropanol) inhibited bradykinin inactivation by plasma, and potentiated its actions “in vitro” and “in vivo” (Ferreira and Rocha e Silva, 1962, 1963; Ferreira et al., 1962; Rocha e Silva, 1963). This venom when added to an isolated guinea pig ileum preparation causes tachyphylactic contractions. Investigating if BAL could potentiate those contractions, we observed that the venom itself had a powerful peptidic potentiating substance, which we named bradykinin potentiating peptide, BPF. As the enzyme that inactivates bradykinin also converts angiotensin in the hypertensive active peptide the structure of BPF was instrumental for the development of the new synthetic family of antihypertensive drugs, named Angiotensin Converting Enzyme Inhibitors.

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Authors and Affiliations

  1. Department of Pharmacology, University of São Paulo, Av. dos Bandeirantes, 3900, Campus USP, 14049-900, Ribeirão Preto, SP, Brazil

    Sérgio Henrique Ferreira

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  1. Sérgio Henrique Ferreira
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Correspondence to Sérgio Henrique Ferreira .

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Editors and Affiliations

  1. , Department of Biological Sciences, National University of Singapore, Science Drive 4 14, Singapore, 117543, Singapore

    R. Manjunatha Kini

  2. , Department of Haematology, University of Berne, Inselspital, Bern, CH-3010, Switzerland

    Kenneth J Clemetson

  3. , Biochemistry and Molecular Biology, University of Southern California, Health Sciences Campus/9270, Los Angeles, 90089, USA

    Francis S. Markland

  4. , Medical Technology, University of Delaware, 305G Willard Hall Educ Bld, Newark, 19716, Delaware, USA

    Mary Ann McLane

  5. , Biochemistry, Meiji Pharmaceutical University, Nishio Kiyose 2-522-1, Tokyo, 204-8588, Japan

    Takashi Morita

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Ferreira, S.H. (2010). From the Bothrops Jararaca Bradykinin Potentiating Peptides to Angiotensin Converting Enzyme Inhibitors. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_2

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