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Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment

1
Department of Neuroscience, Karolinska Institutet; Retzius väg 8, 17177 Stockholm, Sweden
2
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
3
Observatorio Cubano de Neurociencias, Grupo Bohío-Estudio, Zaya 50, 62100 Yaguajay, Cuba
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Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain
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Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, 44121 Ferrara, Italy
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Department of Cell and Molecular Biology, Uppsala University,75105 Uppsala, Sweden
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Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Neuronal Oscillations Lab, Karolinska Institutet, 171 77 Stockholm, Sweden
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Department of Psychiatry, Saitama Medical University, 3388570 Saitama, Japan
9
Department of Anatomy, Histology and Embryology. Faculty of Medicine. Semmelweis University, H-1094 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(6), 1341; https://doi.org/10.3390/molecules23061341
Received: 7 April 2018 / Revised: 22 May 2018 / Accepted: 22 May 2018 / Published: 3 June 2018
(This article belongs to the Special Issue Protein-Protein Interactions)
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. View Full-Text
Keywords: heteroreceptor complexes; G protein-coupled receptors; oligomerization; receptor-receptor interactions; serotonin 5-HT1A receptor; depression; galanin; receptor tyrosine kinase; fibroblast growth factor receptor heteroreceptor complexes; G protein-coupled receptors; oligomerization; receptor-receptor interactions; serotonin 5-HT1A receptor; depression; galanin; receptor tyrosine kinase; fibroblast growth factor receptor
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MDPI and ACS Style

Borroto-Escuela, D.O.; Narváez, M.; Ambrogini, P.; Ferraro, L.; Brito, I.; Romero-Fernandez, W.; Andrade-Talavera, Y.; Flores-Burgess, A.; Millon, C.; Gago, B.; Narvaez, J.A.; Odagaki, Y.; Palkovits, M.; Diaz-Cabiale, Z.; Fuxe, K. Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment. Molecules 2018, 23, 1341. https://doi.org/10.3390/molecules23061341

AMA Style

Borroto-Escuela DO, Narváez M, Ambrogini P, Ferraro L, Brito I, Romero-Fernandez W, Andrade-Talavera Y, Flores-Burgess A, Millon C, Gago B, Narvaez JA, Odagaki Y, Palkovits M, Diaz-Cabiale Z, Fuxe K. Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment. Molecules. 2018; 23(6):1341. https://doi.org/10.3390/molecules23061341

Chicago/Turabian Style

Borroto-Escuela, Dasiel O., Manuel Narváez, Patrizia Ambrogini, Luca Ferraro, Ismel Brito, Wilber Romero-Fernandez, Yuniesky Andrade-Talavera, Antonio Flores-Burgess, Carmelo Millon, Belen Gago, Jose A. Narvaez, Yuji Odagaki, Miklos Palkovits, Zaida Diaz-Cabiale, and Kjell Fuxe. 2018. "Receptor–Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment" Molecules 23, no. 6: 1341. https://doi.org/10.3390/molecules23061341

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