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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
Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden;Univ Urbino Carlo Bo, Dept Biomol Sci, I-61029 Urbino, Italy;Observ Cubano Neurociencias, Grp Bohio Estudio, Zaya 50, Yaguajay 62100, Cuba.
Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
Univ Urbino Carlo Bo, Dept Biomol Sci, I-61029 Urbino, Italy.
Univ Ferrara, SVEB, Dept Life Sci & Biotechnol, I-44121 Ferrara, Italy.
Vise andre og tillknytning
2018 (engelsk)Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 6, artikkel-id 1341Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
2018. Vol. 23, nr 6, artikkel-id 1341
Emneord [en]
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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Identifikatorer
URN: urn:nbn:se:uu:diva-366620DOI: 10.3390/molecules23061341ISI: 000435875400103PubMedID: 29865267OAI: oai:DiVA.org:uu-366620DiVA, id: diva2:1265864
Forskningsfinansiär
The Swedish Brain Foundation, FO2016-0302AFA Insurance, 130328Swedish Society for Medical Research (SSMF), 04X-715Tilgjengelig fra: 2018-11-26 Laget: 2018-11-26 Sist oppdatert: 2018-11-26bibliografisk kontrollert

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