The brain gene expression profile of dopamine D2/D3 receptors and associated signaling proteins following amphetamine self-administration

Sun, Haiguo; Calipari, Erin S.; Beveridge, Thomas J.R.; Chen, R.

doi:10.1016/j.neuroscience.2015.08.053

Cited by 13 publications

(13 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From the perspective of reward, recent work indicates that amphetamine self-administration was more associated with expression of DA D 2 /D 3 receptors in the VTA rather than the nucleus accumbens. 53 Methamphetamine, which acts in part via DAT, also produces a differential impact on DA regulation in the VTA versus NAc 19 and upon TH phosphorylation. 54 …”

Section: Discussionmentioning

confidence: 99%

Regulation of Tyrosine Hydroxylase Expression and Phosphorylation in Dopamine Transporter-Deficient Mice

Salvatore

Calipari

Jones

2016

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Tyrosine hydroxylase (TH) and dopamine transporters (DATs) regulate dopamine (DA) neurotransmission at the biosynthesis and reuptake steps, respectively. Dysfunction or loss of these proteins occurs in impaired locomotor or addictive behavior, but little is known about the influence of DAT expression on TH function. Differences in TH phosphorylation, DA tissue content, L-DOPA biosynthesis, and DA turnover exist between the somatodendritic and terminal field compartments of nigrostriatal and mesoaccumbens pathways. We examined whether differential DAT expression affects these compartmental differences in DA regulation by comparing TH expression and phosphorylation at ser31 and ser40. In heterozygous DAT knockout (KO) (+/−) mice, DA tissue content and DA turnover were unchanged relative to wild-type mice, despite a 40% reduction in DAT protein expression. In DAT KO (−/−) mice, DA turnover increased in all DA compartments, but DA tissue content decreased (90–96%) only in terminal fields. TH protein expression and phosphorylation were differentially affected within DA pathway compartments by relative expression of DAT. TH protein decreased (~74%), though to a significantly lesser extent than DA, in striatum and nucleus accumbens (NAc) in DAT −/− mice, with no decrease in substantia nigra or ventral tegmental area. Striatal ser31 TH phosphorylation and recovery of DA relative to TH protein expression in DAT +/− and DAT −/− mice decreased, whereas ser40 TH phosphorylation increased ~2- to 3-fold in striatum and NAc of DAT −/− mice. These results suggest that DAT expression affects TH expression and phosphorylation largely in DA terminal field compartments, further corroborating evidence for dichotomous regulation of TH between somatodendritic and terminal field compartments of the nigrostriatal and mesoaccumbens pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of Tyrosine Hydroxylase Expression and Phosphorylation in Dopamine Transporter-Deficient Mice

Salvatore

Calipari

Jones

2016

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Changes in RGS protein levels are thus an important molecular mechanism underlying altered Gα-mediated GPCR signaling. We have reported previously that the gene expression of RGS subtypes is sensitive to psychostimulant exposure (Sun et al , 2015). The present study demonstrates that ethanol exposure also significantly influences the expression of RGS proteins in the PFC.…”

Section: Discussionmentioning

confidence: 99%

“…Primers were designed using qPCR primer design software from Integrated DNA Technology and reported previously (Sun et al , 2015). The qPCR was performed using All-in-One qPCR SYBR Green Master Mix (GeneCopoeia Inc., Rockville, MD, USA) in a 96-well format on an ABI PRISM 7500 Fast real-time PCR System (Applied Biosystems, Forester City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, changes in the expression of RGS proteins would influence the duration and strength of receptor-mediated G-protein signaling. It has been shown that the mRNA levels of many RGS subtypes are sensitive to acute and chronic psychostimulant exposure (Sun et al , 2015, Chen Hemby, 2014). Altered levels of RGS proteins are associated with changes in receptor signal transduction and addiction behavior [see review in (Chen & Hemby 2014)].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic intermittent ethanol exposure selectively alters the expression of Gα subunit isoforms and RGS subtypes in rat prefrontal cortex

et al. 2017

Self Cite

View full text Add to dashboard Cite

Chronic alcohol exposure induces pronounced changes in GPCR-mediated G-protein signaling. Recent microarray and RNA-seq analyses suggest associations between alcohol abuse and the expression of genes involved in G-protein signaling. The activity of G-proteins (e.g. Gαi/o and Gαq) is negatively modulated by regulator of G-protein signaling (RGS) proteins which are implicated in drugs of abuse including alcohol. The present study used 7 days of chronic intermittent ethanol exposure followed by 24 hour withdrawal (CIE) to investigate changes in mRNA and protein levels of G-protein subunit isoforms and RGS protein subtypes in rat prefrontal cortex, a region associated with cognitive deficit attributed to excessive alcohol drinking. We found that this ethanol paradigm induced differential expression of Gα subunits and RGS subtypes. For example, there were increased mRNA and protein levels of Gαi1/3 subunits and no changes in the expression of Gαs and Gαq subunits in ethanol-treated animals. Moreover, CIE increased the mRNA but not the protein levels of Gαo. Additionally, a modest increase in Gαi2 mRNA level by CIE was accompanied by a pronounced increase in its protein level. Interestingly, we found that CIE increased mRNA and protein levels of RGS2, RGS4, RGS7 and RGS19 but had no effect on the expression of RGS5, RGS6, RGS8, RGS12 or RGS17. Changes in the expression of Gα subunits and RGS subtypes could contribute to the functional alterations of certain GPCRs following chronic ethanol exposure. The present study suggests that RGS proteins may be potential new targets for intervention of alcohol abuse via modification of Gα-mediated GPCR function.

show abstract

“…was found to be reduced in the ventral tegmental area after 5 days of amphetamine administration [77]. Interestingly, Zhang et al discovered a single nucleotide polymorphism (SNP) in the promoter region of Rgs17 (rs596359) that is associated with substance dependence and results in lower Rgs17 mRNA expression [78].…”

Section: Rgs17: Expression Function and Implications In Cancermentioning

confidence: 99%

Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies

Bodle¹

View full text Add to dashboard Cite

Cancer remains the second leading cause of death in the United States. The complexity of cancer necessitates a constant investigation of cell signaling pathways essential to cancer survival, and the identification of new protein targets for therapeutic development. One family of proteins, Regulator of G Protein Signaling or RGS proteins, has been identified as playing a role in multiple cancers as well as other disease states. The focus of this work is on the identification of chemical compounds that can inhibit the function of two RGS proteins, RGS6 and RGS17. RGS6 has been reported as essential in the development of cardiotoxicity in cancer patients who are treated with the chemotherapeutic doxorubicin. This cardiotoxicity imposes a lifetime dose limit for this drug, one of the most successful chemotherapeutics available. Additionally, RGS6 has been reported as target for the treatment of anxiety, depression, and alcohol dependence. For RGS17, this protein is reported as overexpressed in prostate, lung, breast, and hepatocellular carcinomas, which leads to increased tumor growth and metastatic potential. We use robotic systems to investigate tens of thousands of compounds to identify compounds that inhibit the function of these two proteins. This work details the screening effort, and the validation of compounds discovered including assessing activity in cell culture. We found 2-3 compounds that inhibit RGS6 and 10-20 compounds that inhibit RGS17. We also investigated the selectivity of these compounds for the intended target and investigated how the compounds are doing what they do.

show abstract

The brain gene expression profile of dopamine D2/D3 receptors and associated signaling proteins following amphetamine self-administration

Cited by 13 publications

References 37 publications

Regulation of Tyrosine Hydroxylase Expression and Phosphorylation in Dopamine Transporter-Deficient Mice

Regulation of Tyrosine Hydroxylase Expression and Phosphorylation in Dopamine Transporter-Deficient Mice

Chronic intermittent ethanol exposure selectively alters the expression of Gα subunit isoforms and RGS subtypes in rat prefrontal cortex

Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies

Contact Info

Product

Resources

About