期刊
NATURE
卷 452, 期 7183, 页码 93-U9出版社
NATURE PORTFOLIO
DOI: 10.1038/nature06612
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资金
- Medical Research Council [G9811527] Funding Source: researchfish
- MRC [G9811527] Funding Source: UKRI
The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception(1,2). Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR)(3,4). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia(5-7). The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR(8-10) and resemble some of the core symptoms of schizophrenia(10-12). Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G- protein- coupled receptor family, to form functional complexes in brain cortex. The 2AR - mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen- specific signalling and behavioural responses. In post- mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis.
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