Next Article in Journal
Pomelo Peel Modified with Citrate as a Sustainable Adsorbent for Removal of Methylene Blue from Aqueous Solution
Next Article in Special Issue
14-3-3: A Case Study in PPI Modulation
Previous Article in Journal
Indium-Catalyzed Direct Conversion of Lactones into Thiolactones Using a Disilathiane as a Sulfur Source
Previous Article in Special Issue
Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40–CD154 Costimulatory Protein-Protein Interaction
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessReview
Molecules 2018, 23(6), 1341; https://doi.org/10.3390/molecules23061341

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
4
Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain
5
Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, 44121 Ferrara, Italy
6
Department of Cell and Molecular Biology, Uppsala University,75105 Uppsala, Sweden
7
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Neuronal Oscillations Lab, Karolinska Institutet, 171 77 Stockholm, Sweden
8
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.
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)
Full-Text   |   PDF [1381 KB, uploaded 3 June 2018]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top