RT Journal Article
T1 Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia
A1 Borroto-Escuela, Dasiel O.
A1 Ferraro, Luca
A1 Narvaez, Manuel
A1 Tanganelli, Sergio
A1 Beggiato, Sarah
A1 Liu, Fang
A1 Rivera, Alicia
A1 Fuxe, Kjell
K1 Adenosine receptors
K1 A2A-D2 heteroreceptor complexes
K1 Schizophrenia
K1 Brain
K1 Novel pharmacology
K1 Heterobivalent drugs
K1 Sigma 1 receptor
K1 Receptor de adenosina A2A
K1 Esquizofrenia
K1 Encéfalo
K1 Farmacología
K1 Proteínas del núcleo viral
AB 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.
PB MDPI
YR 2020
FD 2020-04-27
LK http://hdl.handle.net/10668/3840
UL http://hdl.handle.net/10668/3840
LA en
NO Borroto-Escuela DO, Ferraro L, Narvaez M, Tanganelli S, Beggiato S, Liu F, et al. Multiple Adenosine-Dopamine (A2A-D2 Like) Heteroreceptor Complexes in the Brain and Their Role in Schizophrenia. Cells. 2020 Apr 27;9(5):1077
DS RISalud
RD Apr 19, 2025