scholarly journals Heteroreceptor Complexes and their Allosteric Receptor–Receptor Interactions as a Novel Biological Principle for Integration of Communication in the CNS: Targets for Drug Development

2015 ◽  
Vol 41 (1) ◽  
pp. 380-382 ◽  
Author(s):  
Kjell Fuxe ◽  
Dasiel O Borroto-Escuela
Keyword(s):  
Drug Development ◽  
Heteroreceptor Complexes ◽  
Receptor Interactions ◽  
Biological Principle

scholarly journals Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1902
Author(s):  
Dasiel O. Borroto-Escuela ◽  
Patrizia Ambrogini ◽  
Manuel Narvaez ◽  
Valentina Di Liberto ◽  
Sarah Beggiato ◽  
...  
Keyword(s):  
Mental Disease ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Positive Effects ◽  
Heteroreceptor Complexes ◽  
Receptor Interactions ◽  
Mental Diseases ◽  
Biological Principle ◽  
Serotonin Neurons ◽  
Allosteric Mechanisms

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.

Dopamine D2 heteroreceptor complexes and their receptor–receptor interactions in ventral striatum

2014 ◽  
pp. 113-139 ◽  
Author(s):  
Kjell Fuxe ◽  
Dasiel O. Borroto-Escuela ◽  
Alexander O. Tarakanov ◽  
Wilber Romero-Fernandez ◽  
Luca Ferraro ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Heteroreceptor Complexes ◽  
Dopamine D2 ◽  
Receptor Interactions

scholarly journals SY28-5RECEPTOR-RECEPTOR INTERACTIONS IN HETERORECEPTOR COMPLEXES. A NEW CONCEPT IN NEUROPSYCHOPHARMACOLOGY

2015 ◽  
Vol 50 (suppl 1) ◽  
pp. i32.1-i32
Author(s):  
K. Fuxe ◽  
A. Hansson ◽  
D. O. Borroto-Escuela
Keyword(s):  
Heteroreceptor Complexes ◽  
Receptor Interactions
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