期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 39, 期 12, 页码 1008-1020出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2018.10.007
关键词
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资金
- Swedish Medical Research Council [62X-00715-50-3]
- Parkinson Fonden
- Hjarnfonden [F02018-0286]
- Karolinska Institutet Forskningsstiftelser
- Institute of Pharmacology, Polish Academy of Sciences
The concept of allosteric receptor-receptor interactions in G protein-coupled receptor homo-and heteroreceptor complexes in which they physically interact provides a new dimension to molecular integration in the brain. The receptor-receptor interactions dynamically change recognition, pharmacology, signaling, and trafficking of the participating receptors. Among the receptor complexes, disruption of the A2A receptor-dopamine D2 receptor (A2AR-D2R) complex by an A2AR agonist has been shown to fully block the inhibition of cocaine self-administration. Cocaine induced pathological A2AR-D2R-Sigma1R complexes may form a long-term memory with a strong and permanent D2R brake, leading to cocaine addiction. These heteroreceptor complexes can potentially be targeted for future pharmacotherapy of cocaine addiction by using heterobivalent compounds or A2AR-D2R receptor interface-interfering peptides that disrupt the A2AR-D2R-Sigma1R complexes.
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