2026-04-29T04:09:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/184152024-09-21T19:13:11Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Borroto-Escuela, Dasiel O author Ambrogini, Patrizia author Narvaez, Manuel author Di Liberto, Valentina author Beggiato, Sarah author Ferraro, Luca author Fores-Pons, Ramon author Alvarez-Contino, Jose E author Lopez-Salas, Alexander author Mudò, Giuseppa author Díaz-Cabiale, Zaida author Fuxe, Kjell author 2021-07-27 The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biological principle of forming 5-HT and other heteroreceptor complexes in the brain also help understand the mechanism of action for especially the 5-HT hallucinogens, including putative positive effects of e.g., psilocybin and the indicated prosocial and anti-stress actions of MDMA (ecstasy). The GalR1-GalR2 heterodimer and the putative GalR1-GalR2-5-HT1 heteroreceptor complexes are targets for Galanin N-terminal fragment Gal (1-15), a major modulator of emotional networks in models of mental disease. GPCR-receptor tyrosine kinase (RTK) heteroreceptor complexes can operate through transactivation of FGFR1 via allosteric mechanisms and indirect interactions over GPCR intracellular pathways involving protein kinase Src which produces tyrosine phosphorylation of the RTK. The exciting discovery was made that several antidepressant drugs such as TCAs and SSRIs as well as the fast-acting antidepressant drug ketamine can directly bind to the TrkB receptor and provide a novel mechanism for their antidepressant actions. Understanding the role of astrocytes and their allosteric receptor-receptor interactions in modulating forebrain glutamate synapses with impact on dorsal raphe-forebrain serotonin neurons is also of high relevance for research on major depressive disorder. http://hdl.handle.net/10668/18431 http://hdl.handle.net/20.500.12105/18415 34440670 10.3390/cells10081902 2073-4409 Cells G protein-coupled receptors astroglia depression heteroreceptor complexes rapid antidepressant drugs receptor tyrosine kinase serotonin receptors Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia-Relevance for Mental Diseases.