2026-04-29T04:09:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/180372024-11-28T15:28:02Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
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
authoraffiliation
[Borroto-Escuela,DO; Fuxe,K] Department of Neuroscience, Karolinska Institutet, Stockholm , Sweden. [Borroto-Escuela,DO] Observatorio Cubano de Neurociencias, Grupo Bohío-Estudio, Yaguajay, Cuba. [Ferraro,L; Beggiato,S] Department of Life sciences and Biotechnology, University of Ferrara, Ferrara, Italy. [Narvaez,M] Facultad de Medicina, Instituto de Investigacion de Málaga, Universidad de Malaga, Malaga, Spain. [Tanganelli,S] Department of Medical Sciences, University of Ferrara, Ferrara, Italy. [Liu,F] Campbell Research, Centre for Addiction and Mental Health Institute, University of Toronto, Toronto, Canada. [Rivera,A] Department of Cell Biology, University of Malaga, Instituto de Investigación Biomédica (IBIMA), Malaga, Spain.
2024-02-12T19:46:02Z
2024-02-12T19:46:02Z
2020-04-27
http://hdl.handle.net/10668/3840
http://hdl.handle.net/20.500.12105/18037
32349279
10.3390/cells9051077
2073-4409
Cells
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.
eng
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
review article