Calcium and Protein Kinase C Signaling in Response to Vasoactive Peptides in Human Cerebromicrovascular Endothelial Cells

  • Danica B. Stanimirovic
  • Paul Morley
  • Edith Hamel
  • Rita Ball
  • Geoff Mealing
  • Jon P. Durkin
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)


Vasoactive peptides endothelin-1 (ET-1) and bradykinin (BK) were shown to induce immediate increases in intracellular calcium concentrations, [Ca2+]i, and endogenous phosphorylation of the protein kinase C (PKC)-specific substrate, 85 kD MARCKS protein, in human cerebromicrovascular endothelial cells (HBEC). The peptides-induced [Ca2+]i surges were not affected by incubating the cells in Ca2+-free medium or by pretreating them with Ca2+-channel blocker D600 (50 µ;M). BK-stimulated [Ca2+]i increases were completely inhibited, whereas ET-1-induced [Ca2+]i, increases were insensitive to ADP-ribosylation of G-proteins by pertussis toxin. Both peptides-triggered [Ca2+]i, surges and MARCKS protein phosphorylation were abolished by the inhibitor of inositol phospholipid hydrolysis, U73122 (2.5–5 µM).


Pertussis Toxin Vasoactive Peptide Cerebral Endothelial Cell Bovine Brain Microvessel Endothelial Cell Endogenous Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Il est démontré que les peptides vasoactifs, I’endotheline (ET-1) et la bradykinine (BK) induisent une augmentation rapide du calcium intracellulaire, [Ca2+]i, et une phosphorylation endogène du substrat spécifique de la protéine kinase C (PKC), soit la protéine MARCKS de 85 KD, chez les cellules endothéliales cérébromicrovasculaires humaines (HBEC). L’augmentation transitoire du [Ca2+]i induite par ces peptides n’est pas dépendante du calcium extracellulaire et n’est pas affectée par le bloqueur de canaux calciques, le D-600 (500.µM). L’ADP-ribosylation de la protéine G induite par la toxine de pertussis, inhibe complètement l’augmentation du [Ca2+]i stimulée par la BK et n’a aucun effet sur celle provoquée par l’ET-1. La variation du [Ca2+]i produite par ces peptides, de même que la phosphorylation de la protéine MARCKS sont abolies par le U-73122 (2.5–5 µM), un inhibiteur de l’hydrolyse des phosphatidylinositols.


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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Danica B. Stanimirovic
    • 1
  • Paul Morley
    • 1
  • Edith Hamel
    • 2
  • Rita Ball
    • 1
  • Geoff Mealing
    • 1
  • Jon P. Durkin
    • 1
  1. 1.Cellular Neurobiology Group Institute for Biological SciencesNational Research Council of CanadaOttawaCanada
  2. 2.Montreal Neurological InstituteMontrealCanada

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