Prolonged signalling and trafficking of the bradykinin B2 receptor stimulated with the amphibian peptide maximakinin: Insight into the endosomal inactivation of kinins

被引:19
作者
Bawolak, Marie-Therese [1 ]
Roy, Caroline [1 ]
Gera, Lajos [2 ]
Marceau, Francois [1 ]
机构
[1] Univ Laval, CHUQ, Ctr Hosp Univ Quebec, Ctr Rech Rhumatol & Immunol, Quebec City, PQ G1V 4G2, Canada
[2] Univ Colorado Denver, Dept Biochem, Aurora, CO 80045 USA
基金
加拿大健康研究院;
关键词
Maximakinin; Bradykinin B2 receptors; Receptor cycling; Angiotensin converting enzyme; Endosomes; ANGIOTENSIN-CONVERTING ENZYME; PHARMACOLOGICAL PROFILE; DOWN-REGULATION; BOMBINA-MAXIMA; CHINESE TOAD; CELLS; AGONISTS; HYDROLYSIS; ANTAGONIST; EXPRESSION;
D O I
10.1016/j.phrs.2011.11.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Maximakinin, a 19-residue peptide from the amphibian Bombina maxima, incorporates the full sequence of bradykinin (BK) at its C-terminus with a hydrophilic 10-residue N-terminal extension. As a putative venom component, it may stimulate BK B-2 receptors (B(2)Rs) in a distinct manner relative to the fragile mammalian agonist BK. Maximakinin affinity for B(2)Rs and angiotensin converting enzyme (ACE) and its pharmacological profile have been compared to those of BK. Maximakinin is an agonist of the human and rabbit B2R with a 8-12 fold lesser potency, but a prolonged duration of action relative to BK (ERK MAP kinase activation, c-Fos induction in HEK 293 cells). Maximakinin had a moderately inferior affinity (similar to 6-fold vs. BK) for recombinant ACE based on [H-3]enalaprilat binding displacement. Unlike BK, maximakinin induced the internalization of the fusion protein B2R-green fluorescent protein (GFP) and the downregulation of this construction over a 12-h stimulation period, reproducing the effect of inactivation-resistant B2R agonists. Alternate homologues of BK extended at the N-terminus showed intermediate behaviours between BK and maximakinin in the B2R-GFP downregulation assay. The recycling of B2R-GFP at the cell surface after a 3-h BK treatment was notably inhibited by cotreatment with E-64 or bafilomycin A1, supporting that an endosomal cysteine protease degrades kinins in a process that determines the cycling and fate of the B2R. Maximakinin is the first known natural kinin sequence that elicits a prolonged cellular signalling, thus suggesting a possible basis for a venomous action and a naturally selected one for the design of B2R-transported biotechnological cargoes. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:247 / 253
页数:7
相关论文
共 31 条
  • [1] Bachvarov DR, 2001, J PHARMACOL EXP THER, V297, P19
  • [2] B-9972 (D-Arg-[Hyp3, IgI5, Oic7, IgI8]-bradykinin) is an inactivation-resistant agonist of the bradykinin B2 receptor derived from the peptide antagonist B-9430 (D-Arg-[Hyp3, IgI5, D-IgI7, Oic8]-bradykinin):: Pharmacologic profile and effective induction of receptor degradation
    Bawolak, Marie-Therese
    Gera, Lajos
    Morissette, Guillaume
    Stewart, John M.
    Marceau, Francois
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 323 (02) : 534 - 546
  • [3] Bradykinin B2 receptor-mediated transport into intact cells: Anti-receptor antibody-based cargoes
    Bawolak, Marie-Therese
    Lodge, Robert
    Morissette, Guillaume
    Marceau, Francois
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2011, 668 (1-2) : 107 - 114
  • [4] Effects of inactivation-resistant agonists on the signalling, desensitization and down-regulation of bradykinin B2 receptors
    Bawolak, Marie-Therese
    Fortin, Sebastien
    Bouthillier, Johanne
    Adam, Albert
    Gera, Lajos
    Gaudreault, Rene C.
    Marceau, Francois
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2009, 158 (05) : 1375 - 1386
  • [5] Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme
    Brguljan, PM
    Turk, V
    Cimerman, N
    Brzin, J
    Krizaj, I
    Popovic, A
    [J]. PEPTIDES, 2003, 24 (12) : 1977 - 1984
  • [6] ACTION OF RAT-LIVER CATHEPSIN-B ON BRADYKININ AND ON THE OXIDIZED INSULIN A-CHAIN
    BROMME, D
    STEINERT, A
    FITTKAU, S
    KIRSCHKE, H
    [J]. FEBS LETTERS, 1987, 219 (02) : 441 - 444
  • [7] High-level expression and purification of the human bradykinin B2 receptor in a tetracycline-inducible stable HEK293S cell line
    Camponova, Pamela
    Baud, Stephanie
    Mattras, Helene
    Duroux-Richard, Isabelle
    Bonnafous, Jean-Claude
    Marie, Jacky
    [J]. PROTEIN EXPRESSION AND PURIFICATION, 2007, 55 (02) : 300 - 311
  • [8] Cloning of maximakinin precursor cDNAs from Chinese toad, Bombina maxima, venom
    Chen, TB
    Bjourson, AJ
    McClean, S
    Orr, DF
    O'Kane, EJ
    Rao, PF
    Shaw, C
    [J]. PEPTIDES, 2003, 24 (06) : 853 - 861
  • [9] Endosomal Endothelin-converting Enzyme-1 A REGULATOR OF β-ARRESTIN-DEPENDENT ERK SIGNALING
    Cottrell, Graeme S.
    Padilla, Benjamin E.
    Amadesi, Silvia
    Poole, Daniel P.
    Murphy, Jane E.
    Hardt, Markus
    Roosterman, Dirk
    Steinhoff, Martin
    Bunnett, Nigel W.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (33) : 22411 - 22425
  • [10] HYDROLYSIS OF BRADYKININ AND ITS HIGHER HOMOLOGS BY ANGIOTENSIN-CONVERTING ENZYME
    DORER, FE
    RYAN, JW
    STEWART, JM
    [J]. BIOCHEMICAL JOURNAL, 1974, 141 (03) : 915 - 917