| Texto completo | |
| Autor(es): |
Barros, Alexandre J.
[1]
;
Ito, Christian M.
[1]
;
Makino, Elaine N.
[1]
;
Cembranelli, Fernando A. M.
[1]
;
Moraes, Francisco C.
[1]
;
Souza, Sinval E. G.
[1]
;
Oliveira, Laerte
[1]
;
Shimuta, Suma I.
[1]
;
Nakaie, Clovis R.
[1]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, BR-04023062 Sao Paulo - Brazil
Número total de Afiliações: 1
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Biological Chemistry; v. 390, n. 12, p. 1265-1270, DEC 2009. |
| Citações Web of Science: | 1 |
| Resumo | |
Binding of angiotensin II (DRVYIHPF, AngII) to its AT(1) receptor can trigger a process known as tachyphylaxis (loss of receptor response owing to repeated agonist stimulation). We propose a two-state binding model for tachyphylaxis where the N-terminal Asp(1) and Arg(2) residues of the peptide are supposed to initially bind to the N-terminal segment (Arg(23)) and to the EC-3 loop (Asp(281)) of an AT, molecule, respectively (state 1). Sequentially, a disruption of the salt bond between the AngII Asp(1) beta-carboxyl function and the receptor Arg(23) can occur with release of the peptide N-terminal segment, favoring the binding of the Arg(2) residue to the EC-3 loop (Asp(178,281), state 2). In the present study, we expanded this investigation by assaying pharmacological properties of different AngII analogs in guinea-pig ileum bearing modifications at positions 1 and 2. Most of these peptides were weak agonists but many of them had the ability to induce tachyphylaxis. These findings support the two-state model for tachyphylaxis, but alternative mechanisms were revealed where state 1 was no longer needed, depending on the chemical structure of AngII residue 1. Otherwise, any modification of the wild type AngII Arg(2) residue was deleterious for the tachyphylaxis mechanism. (AU) | |
| Processo FAPESP: | 07/56480-0 - Sintese e estudos de peptideos e analogos envolvidos principalmente no sistema renina-angiotensina e calicreina-cinina. |
| Beneficiário: | Clovis Ryuichi Nakaie |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |