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 language | English |
|---|---|
| Pages (from-to) | 113-124 |
| Number of pages | 12 |
| Journal | Biochemical Journal |
| Volume | 428 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - May 15 2010 |
| Externally published | Yes |
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Keywords
- Astrocyte
- Bioluminescence resonance energy transfer
- Calcium
- Cell proliferation
- G-protein
- Urotensin II receptor
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Medicine(all)
Cite this
The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms : Involvement in cell proliferation. / Jarry, Marie; Diallo, Mickaël; Lecointre, Céline; Desrues, Laurence; Tokay, Tursonjan; Chatenet, David; Leprince, Jérôme; Rossi, Oriana; Vaudry, Hubert; Tonon, Marie Christine; Prézeau, Laurent; Castel, Hélène; Gandolfo, Pierrick.
In: Biochemical Journal, Vol. 428, No. 1, 15.05.2010, p. 113-124.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms
T2 - Involvement in cell proliferation
AU - Jarry, Marie
AU - Diallo, Mickaël
AU - Lecointre, Céline
AU - Desrues, Laurence
AU - Tokay, Tursonjan
AU - Chatenet, David
AU - Leprince, Jérôme
AU - Rossi, Oriana
AU - Vaudry, Hubert
AU - Tonon, Marie Christine
AU - Prézeau, Laurent
AU - Castel, Hélène
AU - Gandolfo, Pierrick
PY - 2010/5/15
Y1 - 2010/5/15
N2 - 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.
AB - 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.
KW - Astrocyte
KW - Bioluminescence resonance energy transfer
KW - Calcium
KW - Cell proliferation
KW - G-protein
KW - Urotensin II receptor
UR - http://www.scopus.com/inward/record.url?scp=77953393621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953393621&partnerID=8YFLogxK
U2 - 10.1042/BJ20090867
DO - 10.1042/BJ20090867
M3 - Article
VL - 428
SP - 113
EP - 124
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 1
ER -