2026-07-23T19:37:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/176022024-09-21T18:42:48Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Borroto-Escuela, Dasiel O
author
Narváez, Manuel
author
Ambrogini, Patrizia
author
Ferraro, Luca
author
Brito, Ismel
author
Romero-Fernandez, Wilber
author
Andrade-Talavera, Yuniesky
author
Flores-Burgess, Antonio
author
Millon, Carmelo
author
Gago, Belen
author
Narvaez, Jose Angel
author
Odagaki, Yuji
author
Palkovits, Miklos
author
Diaz-Cabiale, Zaida
author
Fuxe, Kjell
2024-02-08T14:41:27Z
2024-02-08T14:41:27Z
2018-06-03
10.3390/molecules23061341
1420-3049
Molecules (Basel, Switzerland)
http://hdl.handle.net/10668/12542
29865267
http://hdl.handle.net/20.500.12105/17602
Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A⁻FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A⁻FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A⁻5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1⁻15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1⁻GalR2⁻5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.
eng
G protein-coupled receptors
Depression
Fibroblast growth factor receptor
Galanin
Heteroreceptor complexes
Oligomerization
Receptor tyrosine kinase
Receptor-receptor interactions
Serotonin 5-HT1A receptor
Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.
research article