期刊
JOURNAL OF NEUROSCIENCE METHODS
卷 199, 期 2, 页码 258-264出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneumeth.2011.05.021
关键词
Heteromer; Adenosine; Dopamine; Histamine; Cloning; Parkinson's disease
资金
- Spanish Ministerio de Ciencia y Tecnologia [SAF2008-00146]
G-protein-coupled receptors (GPCRs) represent a diverse protein family of receptors that transduce signals from the extracellular surrounding to intracellular signaling molecules evoking various cellular responses. It is now widely accepted that GPCRs are expressed and function as dimers or most probably as oligomers of more than two receptor protomers. The heteromer has different biochemical and pharmacological characteristics from the monomers, which increases the functional responses of GPCRs. GPCRs are involved in many diseases, and are also the target of around half of all modern medicinal drugs. In the case of Parkinson's disease, a degenerative process caused by gradual disappearance of dopaminergic nigrostriatal neurons, it is suspected that the targets for treatment should be dopamine-receptor-containing heteromers. Technologies based on the use of fluorescent- or luminescent-fused receptors and adaptations of resonance energy transfer (RET) techniques have been useful in investigating the functional inter-relationships between receptors in a heteromer. In this study functional recombinant adenosine A(2A)-Rluc, dopamine D(2)-GFP(2) and histamine H(3)-YFP receptor fusion proteins were successfully cloned and characterized, producing the essential basis for heteromerization studies between these receptors. This might provide a better insight into their pharmacological and functional inter-relationships in the brain and enable the design and evaluation of new therapeutic strategies for Parkinson's disease. (C) 2011 Elsevier B.V. All rights reserved.
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