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Träfflista för sökning "WFRF:(Tanganelli S) ;pers:(Rivera A)"

Sökning: WFRF:(Tanganelli S) > Rivera A

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  • Fuxe, K., et al. (författare)
  • Intramembrane receptor-receptor interactions: a novel principle in molecular medicine
  • 2007
  • Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 114:1, s. 49-75
  • Tidskriftsartikel (refereegranskat)abstract
    • In 1980/81 Agnati and Fuxe introduced the concept of intramembrane receptor-receptor interactions and presented the first experimental observations for their existence in crude membrane preparations. The second step was their introduction of the receptor mosaic hypothesis of the engram in 1982. The third step was their proposal that the existence of intramembrane receptor-receptor interactions made possible the integration of synaptic (WT) and extrasynaptic (VT) signals. With the discovery of the intramembrane receptor-receptor interactions with the likely formation of receptor aggregates of multiple receptors, so called receptor mosaics, the entire decoding process becomes a branched process already at the receptor level in the surface membrane. Recent developments indicate the relevance of cooperativity in intramembrane receptor-receptor interactions namely the presence of regulated cooperativity via receptor-receptor interactions in receptor mosaics (RM) built up of the same type of receptor (homo-oligomers) or of subtypes of the same receptor (RM type1). The receptor-receptor interactions will to a large extent determine the various conformational states of the receptors and their operation will be dependent on the receptor composition (stoichiometry), the spatial organization (topography) and order of receptor activation in the RM. The biochemical and functional integrative implications of the receptor-receptor interactions are outlined and long-lived heteromeric receptor complexes with frozen RM in various nerve cell systems may play an essential role in learning, memory and retrieval processes. Intramembrane receptor-receptor interactions in the brain have given rise to novel strategies for treatment of Parkinson's disease (A2A and mGluR5 receptor antagonists), schizophrenia (A2A and mGluR5 agonists) and depression (galanin receptor antagonists). The A2A/D2, A2A/D3 and A2A/mGluR5 heteromers and heteromeric complexes with their possible participation in different types of RM are described in detail, especially in the cortico-striatal glutamate synapse and its extrasynaptic components, together with a postulated existence of A2A/D4 heteromers. Finally, the impact of intramembrane receptor-receptor interactions in molecular medicine is discussed outside the brain with focus on the endocrine, the cardiovascular and the immune systems.
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  • Fuxe, K., et al. (författare)
  • Receptor-receptor interactions within receptor mosaics : Impact on neuropsychopharmacology
  • 2008
  • Ingår i: Brain Research Reviews. - : Elsevier BV. - 0165-0173 .- 1872-6321. ; 58:2, s. 415-452
  • Forskningsöversikt (refereegranskat)abstract
    • Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D-2 receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D-2 RM, located in the dorsal striatopallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D-2 interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D-2/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D-2 signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D-2-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably representing a compensatory up-regulation to counteract the cocaine-induced increases in dopamine D-2 and D-3 signaling. Therefore, A(2A) agonists, through antagonizing D-2 and D-3 signaling within A(2A)/D-2 and A(2)/D-3 RM heteromers in the nucleus accumbens, may be found useful as a treatment for cocaine dependence. Furthermore, antagonistic cannabinoid CB1/D-2 interactions requiring A(2A) receptors have also been discovered and possibly operate in CB1/D-2/A(2A) RM located principally on striatal glutamate terminals but also on some ventral striato-pallidal GABA neurons, thereby opening up a new mechanism for the integration of endocannabinoid, DA and adenosine mediated signals. Thus, A(2A), mGluR5 and/or CB1 receptors can form integrative units with D-2 receptors within RM displaying different compositions, topography and localization. Also galaninR/5-HT1A RM probably participates in the transmission of the ascending 5-hydroxytryptamine neurons, where galanin receptors antagonize 5-HT1A recognition and signaling. Subtype specific galanin receptor antagonists may therefore represent novel antidepressant drugs. These results suggest the importance of a complete understanding of the function of these RM with regard to disease. Ultimately receptor-recepor interactions within RM that modify dopaminergic and serotonergic signaling may give new strategies for treatment of a wide range of diseases associated with altered dopaminergic and serotonergic signaling.
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  • Borroto-Escuela, DO, et al. (författare)
  • Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia
  • 2020
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:5
  • Tidskriftsartikel (refereegranskat)abstract
    • In the 1980s and 1990s, the concept was introduced that molecular integration in the Central Nervous System could develop through allosteric receptor–receptor interactions in heteroreceptor complexes presents in neurons. A number of adenosine–dopamine heteroreceptor complexes were identified that lead to the A2A-D2 heteromer hypothesis of schizophrenia. The hypothesis is based on strong antagonistic A2A-D2 receptor–receptor interactions and their presence in the ventral striato-pallidal GABA anti-reward neurons leading to reduction of positive symptoms. Other types of adenosine A2A heteroreceptor complexes are also discussed in relation to this disease, such as A2A-D3 and A2A-D4 heteroreceptor complexes as well as higher order A2A-D2-mGluR5 and A2A-D2-Sigma1R heteroreceptor complexes. The A2A receptor protomer can likely modulate the function of the D4 receptors of relevance for understanding cognitive dysfunction in schizophrenia. A2A-D2-mGluR5 complex is of interest since upon A2A/mGluR5 coactivation they appear to synergize in producing strong inhibition of the D2 receptor protomer. For understanding the future of the schizophrenia treatment, the vulnerability of the current A2A-D2like receptor complexes will be tested in animal models of schizophrenia. A2A-D2-Simag1R complexes hold the highest promise through Sigma1R enhancement of inhibition of D2R function. In line with this work, Lara proposed a highly relevant role of adenosine for neurobiology of schizophrenia.
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  • Resultat 1-6 av 6

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