Catabolism of vasoactive polypeptides by perfused rat liver |
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Authors: | D R Borges E A Limãos J L Prado A C M Camargo |
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Institution: | (1) Department of Biochemistry and Pharmacology, Escola Paulista de Medicina, Caixa Postal 20372, 01000 São Paulo;(2) Department of Pharmacology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, São Paulo, Brazil;(3) Present address: Chefe de Pesquisas I, Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, Rio de Janeiro |
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Abstract: | Summary Exsanguinated rat liver preparations perfused in situ with oxygenated saline solutions inactivated recirculating bradykinin (BK) at rates of 2.3 to 9.1 and isoleucyl5 angiotensin II (AII) at rates of 2.8 to 15.0 nmolex x min–1 x g–1 of liver, depending on the initial concentration of the peptides in the perfusion fluid (3.1 to 18.9×10–6 M for BK and 8.5 to 17.0×10–6M for AII). On the other hand, at similar concentrations, recirculation of isoleucyl5 Angiotensin I (AI) for 8 min did not lead to decrease of its biological activity when assayed on the isolated rat uterus. Following a single passage through liver, picomole amounts of both BK and AII were inactivated by about 90% as revealed by assays on a superfused rat uterus.The potency ratio AI:AII, assayed on a superfused rat uterus was 1:22 and changed to 1:5 following a single passage of both peptides through liver. This finding and the separation of 4.9% of AII on carboxymethylcellulose columns following recirculation of AI through rat liver indicate a conversion of AI into AII. The dipeptides Phe-Arg, Ser-Pro and Gly-Phe were identified among the hydrolysis products of perfused BK. A peptidyldipeptide hydrolase (EC 3.4.15) may be responsible for both the BK inactivation and AI conversion. The inactivation of AII cannot be attributed to the same enzyme.Abbreviations BK
bradykinin
- AII
isoleucyl5 angiotensin II
- AI
the corresponding angiotensin I
- BPP 5a
bradykinin-potentiating peptide PCA-Lys-Trp-Ala-Pro
Work supported by grants from Project BIOQ/FAPESP (São Paulo) and FINEP (Rio de Janeiro)From Department of Medicine, EPMFrom Department of Physiology and Biophysics, EPM |
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Keywords: | Kinin inactivation Angiotensin inactivation Angiotensin conversion Liver perfusion |
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