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oai:recercat.cat:2445/490872025-12-05T10:08:16Zcom_2072_1057col_2072_478917col_2072_478929

On the existence and function of galanin receptor heteromers in the central nervous system Fuxe, Kjell Borroto Escuela, Dasiel Oscar 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 Receptors de serotonina Sistema nerviós central Proteïnes G Serotonin receptors Central nervous system G Proteins 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 2014-01-22T10:05:24Z 2014-01-22T10:05:24Z 2012-10-26 2014-01-22T10:05:24Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 1664-2392 https://hdl.handle.net/2445/49087 617235 23112793 eng Reproducció del document publicat a: http://dx.doi.org/10.3389/fendo.2012.00127 Frontiers in Endocrinology, 2012, vol. 3, p. 1-12 http://dx.doi.org/10.3389/fendo.2012.00127 cc-by (c) Fuxe, Kjell et al., 2012 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess 12 p. application/pdf Frontiers Media Articles publicats en revistes (Patologia i Terapèutica Experimental)