The kallikrein-kinin system is falling into pieces: bradykinin fragments are biological active peptides
The kallikrein-kinin system is falling into pieces: bradykinin fragments are biological active peptides
ABSTRACT Background and purposeBradykinin [BK-(1-9)] is an endogenous peptide involved in many physiological and pathological processes, such as cardiovascular homeostasis and inflammation. The central dogma of the kallikrein-kinin system is that BK-(1-9) fragments are biologically inactive. In this manuscript, we proposed to test whether these fragments were indeed inactive. Experimental ApproachNitric oxide (NO) was quantified in human, mouse and rat cells loaded with DAF-FM after stimulation with BK-(1-9), BK-(1-7), BK-(1-5) and BK-(1-3). We used adult male rat aortic ring preparation to test vascular reactivity mediated by BK-(1-9) fragments. Changes in blood pressure and heart rate was measured in conscious adult male rats by intraarterial catheter method. Key resultsBK-(1-9) induced NO production in all cell types tested by B2 receptor activation. BK-(1-7), BK-(1-5) and BK-(1-3) also induced NO production in all tested cell types but this response was independent of the activation of B1 receptor and/or B2 receptor. BK-(1-7), BK-(1-5) or BK-(1-3) induced only vasorelaxant effect and in a concentration-dependent fashion. Vasorelaxant effects for BK-(1-7), BK-(1-5) or BK-(1-3) were independent of the kinin receptors. Different administration routes (i.e., intravenous or intra-arterial) did not affect the observed hypotension induced by BK-(1-7), BK-(1-5) or BK-(1-3). Importantly, these observations diverged from the BK-(1-9) results, highlighting that indeed the BK-(1-9) fragments do not seem to act via the classical kinin receptors. Conclusions and implicationsIn conclusion, BK-(1-7), BK-(1-5) and BK-(1-3) are biologically active components of the kallikrein-kinin system. Importantly, observed pathophysiological outcomes of these peptides are independent of B1R and/or B2R activation.
Antunes Ma¨asa Mota、Scalzo J¨2nior S¨|rgio Ricardo Aluotto、Guatimosim Silvia、Souza Santos Robson Augusto、da Rocha Isabella Domingos、Barbosa Cordeiro L¨adia Pereira、Peliky Fontes Marco Ant?nio、Menezes Gustavo Batista、Resende Jarbas Magalh?es、Teixeira Vanessa Pereira、Amaral Fl¨￠vio Almeida、Santos Anderson Kenedy、Souza-Silva Igor Maciel、de Paula Cristiane Amorim、de Oliveira V¨avian Louise Soares、Verano-Braga Thiago
Departamento de Morfologia, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Qu¨amica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Morfologia, Universidade Federal de Minas GeraisDepartamento de Qu¨amica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Bioqu¨amica e Imunologia, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas GeraisDepartamento de Bioqu¨amica e Imunologia, Universidade Federal de Minas GeraisDepartamento de Fisiologia e Biof¨asica, Universidade Federal de Minas Gerais
基础医学生理学生物化学
Antunes Ma¨asa Mota,Scalzo J¨2nior S¨|rgio Ricardo Aluotto,Guatimosim Silvia,Souza Santos Robson Augusto,da Rocha Isabella Domingos,Barbosa Cordeiro L¨adia Pereira,Peliky Fontes Marco Ant?nio,Menezes Gustavo Batista,Resende Jarbas Magalh?es,Teixeira Vanessa Pereira,Amaral Fl¨￠vio Almeida,Santos Anderson Kenedy,Souza-Silva Igor Maciel,de Paula Cristiane Amorim,de Oliveira V¨avian Louise Soares,Verano-Braga Thiago.The kallikrein-kinin system is falling into pieces: bradykinin fragments are biological active peptides[EB/OL].(2025-03-28)[2025-06-06].https://www.biorxiv.org/content/10.1101/2020.09.14.296004.点此复制
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