| 1. |
- Borroto-Escuela, DO, et al.
(författare)
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Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia
- 2016
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Ingår i: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 6:2, s. 77-94
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2– N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of pathological allosteric facilitatory 5-HT2A–D2 interaction increasing D2 protomer signaling. Neurotensin (NTS1)–D2 heterocomplexes also exist in the ventral and dorsal striatum, and likely also in midbrain DA nerve cells as NTS1-D2 autoreceptor complexes where neurotensin produces antipsychotic and propsychotic actions, respectively.
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| 2. |
- Borroto-Escuela, DO, et al.
(författare)
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Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes
- 2016
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Ingår i: Neural plasticity. - : Hindawi Limited. - 1687-5443 .- 2090-5904. ; 2016, s. 4827268-
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Tidskriftsartikel (refereegranskat)abstract
- Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can also be produced at A2AR homocomplexes in these antireward neurons, actions in which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the ventral striatopallidal GABA neurons. It involves a differential cocaine-induced increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration. This is potentially due to differences in composition and allosteric plasticity of these complexes versus those in the ventral striatopallidal neurons.
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| 3. |
- Moser, L., et al.
(författare)
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Plasma cleaning of beryllium coated mirrors
- 2016
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Ingår i: Physica Scripta. - : Institute of Physics Publishing (IOPP). - 0031-8949 .- 1402-4896. ; T167
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Tidskriftsartikel (refereegranskat)abstract
- Cleaning systems of metallic first mirrors are needed in more than 20 optical diagnostic systems from ITER to avoid reflectivity losses. Currently, plasma sputtering is considered as one of the most promising techniques to remove deposits coming from the main wall (mainly beryllium and tungsten). This work presents the results of plasma cleaning of rhodium and molybdenum mirrors exposed in JET-ILW and contaminated with typical tokamak elements (including beryllium and tungsten). Using radio frequency (13.56 MHz) argon or helium plasma, the removal of mixed layers was demonstrated and mirror reflectivity improved towards initial values. The cleaning was evaluated by performing reflectivity measurements, scanning electron microscopy, x-ray photoelectron spectroscopy and ion beam analysis.
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