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Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia
| Content Provider | MDPI |
|---|---|
| Author | Borroto-Escuela, Dasiel O. Ferraro, Luca Narvaez, Manuel Tanganelli, Sergio Beggiato, Sarah Liu, Fang Rivera, Alicia Fuxe, Kjell |
| Copyright Year | 2020 |
| Description | 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. |
| Starting Page | 1077 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells9051077 |
| Journal | Cells |
| Issue Number | 5 |
| Volume Number | 9 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-04-27 |
| Access Restriction | Open |
| Subject Keyword | Cells Psychiatry and Mental Health Adenosine Receptors A2a-d2 Heteroreceptor Complexes Schizophrenia Brain Novel Pharmacology Heterobivalent Drugs Sigma 1 Receptor |
| Content Type | Text |
| Resource Type | Article |
