Diallo, Mickaël; Jarry, Marie; Desrues, Laurence; Castel, Hélène; Chatenet, David 
ORCID: https://orcid.org/0000-0002-7270-4328; Leprince, Jérôme; Vaudry, Hubert; Tonon, Marie-Christine et Gandolfo, Pierrick
(2008).
[Orn5]URP acts as a pure antagonist of urotensinergic receptors in rat cortical astrocytes
Peptides
, vol. 29
, nº 5.
pp. 813-819.
DOI: 10.1016/j.peptides.2007.10.023.
Résumé
Cultured rat astrocytes, which express functional urotensin II (UII)/UII-related peptide (URP) receptors (UT), represent a very suitable model to investigate the pharmacological profile of UII and URP analogs towards native UT. We have recently designed three URP analogs [D-Trp4]URP, [Orn5]URP and [D-Tyr6]URP, that act as UT antagonists in the rat aortic ring bioassay. However, it has been previously reported that UII/URP analogs capable of inhibiting the contractile activity of UII possess agonistic activity on UT-transfected cells. In the present study, we have compared the ability of URP analogs to compete for [125 I]URP binding and to modulate cytosolic calcium concentration ([Ca2+]c) in cultured rat astrocytes. All three analogs displaced radioligand binding: [D-Trp4]URP and [D-Tyr6]URP interacted with high- and low-affinity sites whereas [Orn5]URP only bound high-affinity sites. [D-Trp4]URP and [D-Tyr6]URP both induced a robust increase in [Ca2+]c in astrocytes while [Orn5]URP was totally devoid of activity. [Orn5]URP provoked a concentration-dependent inhibition of URP- and UII-evoked [Ca2+]c increase and a rightward shift of the URP and UII dose-response curves. The present data indicate that [D-Trp4]URP and [D-Tyr6]URP, which act as UII antagonists in the rat aortic ring assay, behave as agonists in the [Ca2+]c mobilization assay in cultured astrocytes, whereas [Orn5]URP is a pure selective antagonist in both rat aortic ring contraction and astrocyte [Ca2+]c mobilization assays.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Urotensin II; Urotensin II-related peptide (URP); UT; antagonists; Cytosolic calcium; Binding; Astrocytes |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 21 juill. 2024 19:03 |
| Dernière modification: | 21 juill. 2024 19:03 |
| URI: | https://espace.inrs.ca/id/eprint/14600 |
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