| Functional assessment of angiotensin II and bradykinin analogues containing the paramagnetic amino acid TOAC. | |
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MedLine Citation:
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PMID: 18182243 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study characterized pharmacologically the functional responses to agonists angiotensin II (AngII) and bradykinin (BK) derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin label at the N-terminal (TOAC1-AngII and TOAC0-BK) and internal (TOAC3-AngII and TOAC3-BK) positions of these vasoactive peptides. Affinity constants of the ligands for AT1 and B2 receptors were evaluated in vitro by binding assays and biological effects by extracellular acidification rates and in vivo by blood pressure responses. In contrast to internally labeled analogues (TOAC3-AngII or TOAC3-BK), the TOAC1-AngII and TOAC0-BK derivatives dose-dependently increased the extracellular acidification rate in adherent cultured Chinese hamster ovary (CHO) cells expressing AT1 or B2 receptors, respectively. In addition, TOAC(1)-AngII induced an increase in blood pressure when injected intravenously in awaken rats although with a potency four times smaller when compared to native AngII. Similarly to BK, TOAC0-BK dose-dependently decreased blood pressure when injected intra-arterially in rats with a lower potency when compared to the native peptide. On the contrary, TOAC3-AngII or TOAC3-BK did not provoke any alteration in blood pressure levels. In summary, our results confirmed that the insertion of TOAC-probe in the N-terminal region of peptides does not significantly modify the affinity or biological activity in vitro and in vivo conditions and could be an important tool to evaluate peptide-receptor interaction mechanism. Conversely, possibly due to the unique bend-inducing property of the cyclic TOAC probe, its insertion at position 3 in both AngII and BK structures seems to restrict the interaction and the activation of the AT1 and B2 receptors. |
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Authors:
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Edson L Santos; Kely de Picoli Souza; Regiane A Sabatini; Renan P Martin; Liliam Fernandes; Daniela T Nardi; Luciana Malavolta; Suma I Shimuta; Clóvis R Nakaie; João B Pesquero |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-08-21 |
Journal Detail:
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Title: International immunopharmacology Volume: 8 ISSN: 1567-5769 ISO Abbreviation: Int. Immunopharmacol. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-01-09 Completed Date: 2008-04-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100965259 Medline TA: Int Immunopharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 293-9 Citation Subset: IM |
Affiliation:
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Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, 04023-062 São Paulo, SP, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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analogs & derivatives*,
pharmacology Animals Blood Pressure / drug effects Bradykinin / analogs & derivatives*, pharmacology CHO Cells Cricetinae Cricetulus Cyclic N-Oxides / pharmacology* Male Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Cyclic N-Oxides; 11128-99-7/Angiotensin II; 15871-57-5/2,2,6,6-tetramethylpiperidine-N-oxide-4-amino-4-carboxylic acid; 58-82-2/Bradykinin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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