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Peptide fragments of bradykinin show unexpected biological activity not mediated by B 1 or B 2 receptors

2022; Wiley; Volume: 179; Issue: 12 Linguagem: Inglês

10.1111/bph.15790

1476-5381

Igor Maciel Souza‐Silva, Cristiane Amorim de Paula, Lucas Bolais‐Ramos, Anderson K. Santos, Filipe Alex da Silva, Vívian Louise Soares de Oliveira, Isabella Domingos da Rocha, Maísa Mota Antunes, Lídia Pereira Barbosa Cordeiro, Vanessa Pereira Teixeira, Sérgio Scalzo, Adriana Campezatto Raabe, Pedro Pires Goulart Guimarães, Flávio A. Amaral, Jarbas M. Resende, Marco Antônio Peliky Fontes, Gustavo Batista Menezes, Sílvia Guatimosim, Robson A.S. Santos, Thiago Verano‐Braga,

Urticaria and Related Conditions

Background and Purpose Bradykinin (BK‐(1–9)) is an endogenous nonapeptide involved in multiple physiological and pathological processes. Peptide fragments of bradykinin are believed to be biologically inactive. We have now tested the two major peptide fragments of bradykinin in human and animals. Experimental Approach BK peptides were quantified by MS in male rats. NO release was quantified from human, mouse and rat cells loaded with DAF‐FM. Rat aortic rings were used to measure vascular reactivity. Changes in BP and HR were measured in conscious male rats. To evaluate pro‐inflammatory effects both vascular permeability and nociception were measured in adult mice. Key Results BK‐(1–7) and BK‐(1–5) are produced in vivo from BK‐(1–9). Both peptides induced NO production in all cell types tested. However, unlike BK‐(1–9), NO production elicited by BK‐(1–7) or BK‐(1–5) was not inhibited by B 1 or B 2 receptor antagonists. BK‐(1–7) and BK‐(1–5) induced concentration‐dependent vasorelaxation of aortic rings, without involvement of B 1 or B 2 receptors. Intravenous or intra‐arterial administration of BK‐(1–7) or BK‐(1–5) induced similar hypotensive response in vivo . Nociceptive responses of BK‐(1–7) and BK‐(1–5) were reduced compared to BK‐(1–9), and no increase in vascular permeability was observed for BK‐(1–9) fragments. Conclusions and Implications BK‐(1–7) and BK‐(1–5) are endogenous peptides present in plasma. BK‐related peptide fragments show biological activity, not mediated by B 1 or B 2 receptors. These BK fragments could constitute new, active components of the kallikrein–kinin system.