Looking for the role of cannabinoid receptor heteromers in striatal function

NEUROPHARMACOLOGY

卷:56

Review

Ferre, Sergi¹  Goldberg, Steven R.¹  Lluis, Carme²  Franco, Rafael² 

[1] NIDA, Intramural Res Program, Biomed Res Ctr, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA

[2] Univ Barcelona, Dept Biochem & Mol Biol, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Inst Invest Biomed August Pi & Sunyer,Fac Biol, E-08028 Barcelona, Spain

关键词: Local module;    Receptor heteromers;    Cannabinoid CB1 receptor;    Dopamine D-2 receptor;    Adenosine A(2A) receptor;    mu Opioid receptor;    Striatum;   

DOI  :  10.1016/j.neuropharm.2008.06.076

来源: Elsevier

【 摘 要 】

The introduction of two concepts, local module and receptor heteromer, facilitates the understanding of the role of interactions between different neurotransmitters in the brain. In artificial cell systems, cannabinoid CB, receptors form receptor heteromers with dopamine D-2, adenosine A(2A) and mu opioid receptors. There is indirect but compelling evidence for the existence of the same CB, receptor heteromers in striatal local modules centered in the dendritic spines of striatal GABAergic efferent neurons, particularly at a postsynaptic location. Their analysis provides new clues for the role of endocannabinoids in striatal function, which cannot only be considered as retrograde signals that inhibit neurotransmitter release. Recent studies using a new method to detect heteromerization of more than two proteins, which consists of sequential BRET-FRET (SRET) analysis, has demonstrated that CB1, D-2 and A(2A) receptors can form heterotrimers in transfected cells. It is likely that functional CB1-A(2A)-D-2 receptor heteromers can be found where they are highly co-expressed, in the dendritic spines of GABAergic enkephalinergic neurons. The functional properties of these multiple receptor heteromers and their role in striatal function need to be determined. Published by Elsevier Ltd.

【 授权许可】

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