The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: Involvement in cell proliferation

Marie Jarry, Mickaël Diallo, Céline Lecointre, Laurence Desrues, Tursonjan Tokay, David Chatenet, Jérôme Leprince, Oriana Rossi, Hubert Vaudry, Marie Christine Tonon, Laurent Prézeau, Hélène Castel, Pierrick Gandolfo

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

UII (urotensin II) and its paralogue URP (UII-related peptide) are two vasoactive neuropeptides whose respective central actions are currently unknown. In the present study, we have compared the mechanism of action of URP and UII on cultured astrocytes. Competition experiments performed with [ 125I]UII showed the presence of very-high- and high-affinity binding sites for UII, and a single high-affinity site for URP. Both UII and URP provoked a membrane depolarization accompanied by a decrease in input resistance, stimulated the release of endozepines, neuropeptides specifically produced by astroglial cells, and generated an increase in [Ca 2+]c (cytosolic Ca2+ concentration). The UII/URP-induced [Ca2+]c elevation was PTX (pertussis toxin)-insensitive, and was blocked by the PLC (phospholipase C) inhibitor U73122 or the InsP3 channel blocker 2-APB (2- aminoethoxydiphenylborane). The addition of the Ca2+ chelator EGTA reduced the peak and abolished the plateau phase, whereas the T-type Ca 2+ channel blocker mibefradil totally inhibited the Ca2+ response evoked by both peptides. However, URP and UII induced a monoand bi-phasic dose-dependent increase in [Ca2+]c and provoked short- and long-lasting Ca2+ mobilization respectively. Similar mono- and bi-phasic dose-dependent increases in [3H]inositol incorporation into polyphosphoinositides in astrocytes was obtained, but the effect of UII was significantly reduced by PTX, although BRET (bioluminescence resonance energy transfer) experiments revealed that both UII andURP recruited G αo-protein. Finally, UII, but not URP, exerted a dose-dependent mitogenic activity on astrocytes. Therefore we described that URP and UII exert not only similar, but also divergent actions on astrocyte activity, with UII exhibiting a broader range of activities at physiological peptide concentrations.

Original languageEnglish
Pages (from-to)113-124
Number of pages12
JournalBiochemical Journal
Volume428
Issue number1
DOIs
Publication statusPublished - May 15 2010

Keywords

  • Astrocyte
  • Bioluminescence resonance energy transfer
  • Calcium
  • Cell proliferation
  • G-protein
  • Urotensin II receptor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: Involvement in cell proliferation'. Together they form a unique fingerprint.

  • Cite this

    Jarry, M., Diallo, M., Lecointre, C., Desrues, L., Tokay, T., Chatenet, D., Leprince, J., Rossi, O., Vaudry, H., Tonon, M. C., Prézeau, L., Castel, H., & Gandolfo, P. (2010). The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: Involvement in cell proliferation. Biochemical Journal, 428(1), 113-124. https://doi.org/10.1042/BJ20090867