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Review
. 2015 Jun 19;16(6):14109-21.
doi: 10.3390/ijms160614109.

Novel Therapeutic GPCRs for Psychiatric Disorders

Hidetoshi Komatsu  1
Affiliations
Review

Novel Therapeutic GPCRs for Psychiatric Disorders

Hidetoshi Komatsu. Int J Mol Sci. .

Abstract

G protein-coupled receptors (GPCRs) are the most common targets of the neuropharmacological drugs in the central nervous system (CNS). GPCRs are activated by manifold neurotransmitters, and their activation in turn evokes slow synaptic transmission. They are deeply involved in multiple neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. In the brain, the striatum is strongly innervated by the ventral tegmental area (VTA) and plays a central role in manifestation of psychiatric disorders. Recently, anatomical and comprehensive transcriptome analysis of the non-odorant GPCR superfamily revealed that the orphan GPCRs GPR88, GPR6, and GPR52, as well as dopamine D1 and D2 receptors and the adenosine A2a receptor, are the most highly enriched in the rodent striatum. Genetically engineered animal models and molecular biological studies have suggested that these striatally enriched GPCRs have a potential to be therapeutic psychiatric receptors. This review summarizes the current understanding of the therapeutic GPCR candidates for psychiatric disorders.

Keywords: GPCR; GPR52; GPR6; GPR88; dopamine receptors; psychiatric disorders; schizophrenia; striatum.

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Figures

Figure 1
Figure 1
Striatal-enriched GPCRs in medium-sized spiny neurons (MSNs) in striatum. MSNs can be divided into two types of neurons: striatonigral (left) and striatopallidal MSNs (right). Gs-coupled receptors including D1, GPR52, GPR6, and A2a receptors raise intracellular cAMP concentration which can be reduced by Gi/o-coupled receptors including D2 and GPR88.
Figure 2
Figure 2
Proposed GPR52 signal transduction. GPR52 activation counteracts Gi/o-coupled D2 receptors in striatopallidal neurons (left); and potentiates NMDA activity through phosphorylation of the NMDA receptor via cAMP/PKA, as seen in D1 receptor-NMDA signal transduction (right).
See this image and copyright information in PMC

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