Identification of a serotonin/glutamate receptor complex implicated in psychosis

Article

关键词: METABOTROPIC GLUTAMATE RECEPTORS;    CRYSTAL-STRUCTURE;    SCHIZOPHRENIA;    MODEL;    RHODOPSIN;    AGONIST;    PSILOCYBIN;    OLIGOMERIZATION;    ALIGNMENT;    BINDING;   

DOI  :  10.1038/nature06612

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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