RT Journal Article
T1 Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.
A1 Borroto-Escuela, Dasiel O
A1 Narváez, Manuel
A1 Ambrogini, Patrizia
A1 Ferraro, Luca
A1 Brito, Ismel
A1 Romero-Fernandez, Wilber
A1 Andrade-Talavera, Yuniesky
A1 Flores-Burgess, Antonio
A1 Millon, Carmelo
A1 Gago, Belen
A1 Narvaez, Jose Angel
A1 Odagaki, Yuji
A1 Palkovits, Miklos
A1 Diaz-Cabiale, Zaida
A1 Fuxe, Kjell
K1 G protein-coupled receptors
K1 depression
K1 fibroblast growth factor receptor
K1 galanin
K1 heteroreceptor complexes
K1 oligomerization
K1 receptor tyrosine kinase
K1 receptor-receptor interactions
K1 serotonin 5-HT1A receptor
AB 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.
YR 2018
FD 2018-06-03
LK http://hdl.handle.net/10668/12542
UL http://hdl.handle.net/10668/12542
LA en
DS RISalud
RD Apr 10, 2025