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Biochemical and functional characterization of high-affinity urotensin II receptors in rat cortical astrocytes

Castel, Hélène; Diallo, Mickaël; Chatenet, David ORCID logoORCID: https://orcid.org/0000-0002-7270-4328; Leprince, Jérôme; Desrues, Laurence; Schouft, Marie-Thérèse; Fontaine, Marc; Dubessy, Christophe; Lihrmann, Isabelle; Scalbert, Elizabeth; Malagon, Maria; Vaudry, Hubert; Tonon, Marie-Christine et Gandolfo, Pierrick (2006). Biochemical and functional characterization of high-affinity urotensin II receptors in rat cortical astrocytes Journal of Neurochemistry , vol. 99 , nº 2. pp. 582-595. DOI: 10.1111/j.1471-4159.2006.04130.x.

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Résumé


The urotensin II (UII) gene is primarily expressed in the central nervous system, but the functions of UII in the brain remain elusive. Here, we show that cultured rat astrocytes constitutively express the UII receptor (UT). Saturation and competition experiments performed with iodinated rat UII ([(125)I]rUII) revealed the presence of high- and low-affinity binding sites on astrocytes. Human UII (hUII) and the two highly active agonists hUII(4-11) and [3-iodo-Tyr9]hUII(4-11) were also very potent in displacing [(125)I]rUII from its binding sites, whereas the non-cyclic analogue [Ser5,10]hUII(4-11) and somatostatin-14 could only displace [(125)I]rUII binding at micromolar concentrations. Reciprocally, rUII failed to compete with [(125)I-Tyr0,D-Trp8]somatostatin-14 binding on astrocytes. Exposure of cultured astrocytes to rUII stimulated [(3)H]inositol incorporation and increased intracellular Ca(2+) concentration in a dose-dependent manner. The stimulatory effect of rUII on polyphosphoinositide turnover was abolished by the phospholipase C inhibitor U73122, but only reduced by 56% by pertussis toxin. The GTP analogue Gpp(NH)p caused its own biphasic displacement of [(125)I]rUII binding and provoked an affinity shift of the competition curve of rUII. Pertussis toxin shifted the competition curve towards a single lower affinity state. Taken together, these data demonstrate that rat astrocytes express high- and low-affinity UII binding sites coupled to G proteins, the high-affinity receptor exhibiting the same pharmacological and functional characteristics as UT.

Type de document: Article
Mots-clés libres: astrocytes; G-protein-coupled receptor; urotensin II; urotensin II receptor
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 22 oct. 2024 19:44
Dernière modification: 22 oct. 2024 19:44
URI: https://espace.inrs.ca/id/eprint/14469

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