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|Title:||Essential role of TM V and VI for binding the C-terminal sequences of Des-Arg-kinins|
|Authors:||Santos, Edson L. [UNIFESP]|
Souza, Kely de Picoli [UNIFESP]
Oliveira, Suzana M. [UNIFESP]
Costa-Neto, Claudio M.
Oliveira, Laerte [UNIFESP]
Pesquero, Joao B. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Max Delbruck Ctr Mol Med
kinin B-1 receptor
|Citation:||International Immunopharmacology. Amsterdam: Elsevier B.V., v. 8, n. 2, p. 282-288, 2008.|
|Abstract:||In the kallikrein-kinin and renin-angiotensin systems the main receptors, B-1 and B-2 (kinin receptors) and AT(1) and AT(2) (angiotensin receptors) respectively, are seven-transmembrane domain G-protein-coupled receptors. Considering that the B, agonists Des-Arg(9)-BK (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe), Lys-desArg(9)-BK or Des-Arg(10)-KD (Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe) and the AT, agonist (Asp-Arg-Val-Tyr-lle-His-Pro-Phe) have the same two residues at the C-terminal region (i.e. Pro-Phe), we hypothesized that TM V and TM VI of the B-1 receptor could play an essential role in agonist binding and activity, being these regions receptor sites for binding the C-terminal sequences of Des-Arg-kinins similarly to that observed to AT, receptor. To investigate this hypothesis, we replaced Arg(212) for Ala at the top of the TM V and the sequence 274-282 (CPYHFFAFL) in TM VI of the rat kinin B, receptor by the 32 receptor homologous sequence, 289-297 (FPFQISTFL) and subsequently analyzed the consequences of these mutations by competition binding and functional assays. Despite correct expression, observed at the mRNA and protein level by RT-PCR and confocal microscopy, respectively, no agonist binding and function was verified for the mutated receptors. Therefore, our results suggest an important role for Arg(212) in the TM V and a region of TM VI of rat B, receptor in the interaction with the C-terminal residues of Des-Arg-kinins, similar to that observed with AngII. (c) 2007 Elsevier B.V. All rights reserved.|
|Appears in Collections:||Em verificação - Geral|
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