title: The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: involvement in cell proliferation.
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 [Ca2+]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 Ca2+ channel blocker mibefradil totally inhibited the Ca2+ response evoked by both peptides. However, URP and UII induced a mono- and 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 and URP recruited Galphao-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.
authors.affiliation: EA4310, Inserm U982, DC2N, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation, Astrocyte and Vascular Niche, European Institute for Peptide Research (IFRMP 23), University of Rouen, Mont-Saint-Aignan, Normandy, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Jarry
authors.forename: Mickaël
authors.initials: M
authors.lastname: Diallo
authors.forename: Céline
authors.initials: C
authors.lastname: Lecointre
authors.forename: Laurence
authors.initials: L
authors.lastname: Desrues
authors.forename: Tursonjan
authors.initials: T
authors.lastname: Tokay
authors.forename: David
authors.initials: D
authors.lastname: Chatenet
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.forename: Oriana
authors.initials: O
authors.lastname: Rossi
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Tonon
authors.forename: Laurent
authors.initials: L
authors.lastname: Prézeau
authors.forename: Hélène
authors.initials: H
authors.lastname: Castel
authors.forename: Pierrick
authors.initials: P
authors.lastname: Gandolfo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D049109:Cell Proliferation; D036361:Peptide Hormones / Q000378:metabolism*; D051381:Rats; D014579:Urotensins / Q000378:metabolism*
chemical_list: D036361:Peptide Hormones; D014579:Urotensins; C479081:urotensin II-related peptide, rat; C029677:urotensin II