Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser6]-Bradykinin (pS6-BK)

Diego M. Assis, Luiz Juliano, Thaysa Paschoalin, Maria Kouyoumdjian, Joao B. Calixto, Robson A S Santos, Thelma A. Pertinhez, Francis Gauthier, Thierry Moreau, Michael Blaber, Maria A. Juliano

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Phosphorylated kininogen and some of its fragments containing serine phosphorylated bradykinin ([pS6]-Bk) were identified in human serum and plasma by a phosphoproteomic approach. We report the kininogenase ability of human tissue and plasma kallikreins and tryptase to generate [pS6]-Bk or Lys-[pS6]-Bk having as substrate the synthetic human kininogen fluorescent fragment Abz-MISLMKRPPGF[pS386]PFRSSRI-NH2. The pharmacological assays of [pS6]-Bk showed it as a full B2 bradykinin receptor agonist in smooth muscle, it produces a portal liver hypertensive response in rat and mouse paw edema that lasts longer than Bk. The rat hypotensive response to infusions of Bk is greater than that of [pS6]Bk, both if injected through femoral vein or aorta. [pS6]-Bk was more resistant than Bk to kininase digestion performed with angiotensin converting enzyme, neprilysin, thimet oligopeptidase, aminopeptidase P and carboxypeptidase M. 1H-NMR experiments indicated that [pS6]-Bk has lower flexibility, with the pS6-P7 bond restricted to the trans conformation, and can explain [pS6]-Bk resistance to hydrolysis. In conclusion, [pS6]-Bk presenting lower activity than Bk, with longer lasting effects and being slowly released by kininogenases from synthetic Abz-MISLMKRPPGF[pS386]PFRSSRI-NH2, suggests that phosphorylation of the kininogens can be an efficient kallikrein-kinin system regulator.

Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalBiochemical Pharmacology
Volume97
Issue number2
DOIs
Publication statusPublished - Sep 15 2015

Fingerprint

Kininogens
Kallikreins
Bradykinin
Hydrolysis
Peptide Hydrolases
Pharmacology
thimet oligopeptidase
Rats
Bradykinin B2 Receptors
Plasma Kallikrein
Kallikrein-Kinin System
CD13 Antigens
Tissue Kallikreins
Tryptases
Neprilysin
Kinins
Phosphorylation
Femoral Vein
Peptidyl-Dipeptidase A
Liver

Keywords

  • Kallikreins
  • Kinin
  • Kininogen
  • Peptidase
  • Peptides
  • Protease
  • Tryptase

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry
  • Medicine(all)

Cite this

Assis, D. M., Juliano, L., Paschoalin, T., Kouyoumdjian, M., Calixto, J. B., Santos, R. A. S., ... Juliano, M. A. (2015). Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser6]-Bradykinin (pS6-BK). Biochemical Pharmacology, 97(2), 203-214. https://doi.org/10.1016/j.bcp.2015.07.033

Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser6]-Bradykinin (pS6-BK). / Assis, Diego M.; Juliano, Luiz; Paschoalin, Thaysa; Kouyoumdjian, Maria; Calixto, Joao B.; Santos, Robson A S; Pertinhez, Thelma A.; Gauthier, Francis; Moreau, Thierry; Blaber, Michael; Juliano, Maria A.

In: Biochemical Pharmacology, Vol. 97, No. 2, 15.09.2015, p. 203-214.

Research output: Contribution to journalArticle

Assis, DM, Juliano, L, Paschoalin, T, Kouyoumdjian, M, Calixto, JB, Santos, RAS, Pertinhez, TA, Gauthier, F, Moreau, T, Blaber, M & Juliano, MA 2015, 'Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser6]-Bradykinin (pS6-BK)', Biochemical Pharmacology, vol. 97, no. 2, pp. 203-214. https://doi.org/10.1016/j.bcp.2015.07.033
Assis DM, Juliano L, Paschoalin T, Kouyoumdjian M, Calixto JB, Santos RAS et al. Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser6]-Bradykinin (pS6-BK). Biochemical Pharmacology. 2015 Sep 15;97(2):203-214. https://doi.org/10.1016/j.bcp.2015.07.033
Assis, Diego M. ; Juliano, Luiz ; Paschoalin, Thaysa ; Kouyoumdjian, Maria ; Calixto, Joao B. ; Santos, Robson A S ; Pertinhez, Thelma A. ; Gauthier, Francis ; Moreau, Thierry ; Blaber, Michael ; Juliano, Maria A. / Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser6]-Bradykinin (pS6-BK). In: Biochemical Pharmacology. 2015 ; Vol. 97, No. 2. pp. 203-214.
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