Published August 1979 | Version v1
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Importance of the terminal α-amino group of bradykinin and some kynins on capillary permeability increase

Description

A simple and reliable method is described for the quantitative evaluation of vascular permeability increase induced by vasoactive drugs with Evans blue labelled with iodine-125 or 131. By using this method the importance of α-amino group of bradykinin (Bk), kallidin (Kd) and methionyl-kallidin (Met-Kd) on the biological activity were studied after reacting the kinins with pyridoxal 5'-phosphate followed by reduction with sodium borohydride. Phosphopyridoxyl-kinins were formed leaving free the guanidino groups. Aminoacid analysis of phosphopyridoxyl-kinin showed that the efficiency of the reaction was extremely good in the blockage of α-amino groups [phosphopyridoxyl-bradikinin (PP-Bk) = 98,8%, phosphopyridoxyl-kallidin (PP-Kd) = 95,2%, phosphopyridoxyl-methionyl-kallidin (PP-Met-Kd) = 98,0%. Log dose-response curves were obtained for Bk, Kd, Met-Kd, acetyl-bradykinin (Ac-Bk), PP-Bk, PP-Kd and PP-Met-Kd and the relative potencies calculated through the Lineweaver-Burk plots. The relative potencies were: PP-Bk about 16% the activity of Bk, Ac-Bk about 31% the activity of Bk, PP-Kd about 17% the activity of Kd, PP-Met-Kd about 12% the activity of Met-Kd. The results show that the terminal α-amino group of kinins is important in the mechanisms of biological activity. (Author)

Availability note (English)

MF available from INIS under the Report Number.

Abstract (Portuguese)

Um metodo simples e eficaz foi desenvolvido para quantificacao do aumento da permeabilidade capilar na parede abdominal de rato, a partir do extravasamento do azul de Evans marcado com iodo-125 ou 131, apos administracao intradermica de solucao de substancias vasoativas. Utilizando-se esta metodologia, foi estudada a importancia do grupo α-anino N-terminal das moleculas de bradicinina (Bk), calidina (Kd) e metionilcalidina (Met-Kd) na permeabilidade capilar apos reacao com piridoxal 5'-fosfato seguida de reducao com borohidreto de sodio. Ha formacao de uma base de Schiff com o grupo α-amino N-termal transformando-se apos reducao, em derivados estaveis da fosfopiridoxil-cininas, deixando intacto o radical guanidina. A analise dos residuos de aminoacidos dos derivados fosfopiridoxil-cininas mostrou que a quase totalidade dos α-amino grupos N-terminais se acha bloqueada pelo radical fosfopiridoxila [fosfopiridoxil-bradicinina (PP-Bk) = 98,8%; fosfopiridoxil-calidina (PP-Kd) = 95,2%; e fosfopiridoxil-metionilcalidina (PP-Met-Kd) = 98,9%]. Foram determinadas curvas de atividade para Bk, Kd, Met-Kd, acetil-bradicinina (Ac-Bk), PP-Bk, PP-Kd e PP-Met-Kd. As potencias relativas foram calculadas aplicando-se a representacao grafica de Linweaver-Burk (PP-Bk cerca de 16% de atividade de Bk, Ac-Bk cerca de 31% da atividade de Bk, PP-Kd cerca de 17% da atividade de Kd, e PP-Met-Kd cerca de 12% da atividade de Met-Kd). Os resultados mostram a importancia do grupo α-amino N-terminal livre das cininas nos mecanismos de acao biologica. (Autor)

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Additional details

Additional titles

Original title (Portuguese)
Importancia do grupo α-amino terminal da bradicinina e cininas relacionadas sobre o aumento da permeabilidade capilar

Publishing Information

Imprint Pagination
49 p.
Journal Issue
no. 139
Series
IEA Dissertacao e Tese.
Report number
IEA-DT--139