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oai:repisalud.isciii.es:20.500.12105/180372024-11-28T15:28:02Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Borroto-Escuela, Dasiel O. author Ferraro, Luca author Narvaez, Manuel author Tanganelli, Sergio author Beggiato, Sarah author Liu, Fang author Rivera, Alicia author Fuxe, Kjell author 2020-04-27 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. http://hdl.handle.net/10668/3840 http://hdl.handle.net/20.500.12105/18037 32349279 10.3390/cells9051077 2073-4409 Cells Adenosine receptors A2A-D2 heteroreceptor complexes Schizophrenia Brain Novel pharmacology Heterobivalent drugs Sigma 1 receptor Receptor de adenosina A2A Esquizofrenia Encéfalo Farmacología Proteínas del núcleo viral Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia