Título:
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On the existence and function of galanin receptor heteromers in the central nervous system
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Autor/a:
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Fuxe, Kjell; Borroto-Escuela, Dasiel O.; Romero Fernández, Wilber; Tarakanov, Alexander O.; Calvo, Feliciano; Garriga, Pere; Tena, Mercé; Narváez, Manuel; Millón, Carmelo; Parrado, Concepción; Ciruela Alférez, Francisco; Agnati, Luigi F.; Narváez, José A.; Díaz Cabiale, Zaida
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Otros autores:
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Universitat de Barcelona |
Abstract:
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Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression |
Materia(s):
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-Receptors de serotonina -Sistema nerviós central -Proteïnes G -Serotonin receptors -Central nervous system -G Proteins |
Derechos:
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cc-by (c) Fuxe, Kjell et al., 2012
http://creativecommons.org/licenses/by/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Frontiers Media
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