Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors

Khan, Muhammad Zahid; He, Ling

doi:10.1007/s00213-017-4586-9

Cited by 43 publications

(28 citation statements)

References 303 publications

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“…Gpr26 is an orphan G-protein coupled receptor that is coupled to G s and for which an endogenous ligand is not known 60 . Studies with Gpr26 knockout mice have implicated this receptor in anxiety, depression-like behaviors and obesity, but no known role in pain is known 61 .…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Chamessian

Young

Qadri

et al. 2018

Sci Rep

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The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice. Using RNA-sequencing (RNA-seq), we uncovered more than 13,000 genes. Differential gene expression analysis revealed more than 900 genes with at least 2-fold enrichment. In addition to many known dorsal horn genes, we identified and validated several novel transcripts from pharmacologically tractable functional classes: Carbonic Anhydrase 12 (Car12), Phosphodiesterase 11 A (Pde11a), and Protease-Activated Receptor 3 (F2rl2). In situ hybridization of these novel genes showed differential expression patterns in the SDH, demonstrating the presence of transcriptionally distinct subpopulations within the SST population. Overall, our findings provide new insights into the gene repertoire of SST dorsal horn neurons and reveal several novel targets for pharmacological modulation of this pain-mediating population and treatment of pathological pain.

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Section: Resultsmentioning

confidence: 99%

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Chamessian

Young

Qadri

et al. 2018

Sci Rep

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“…For example, indoxyl sulfate, kynurenine and kynurenate signal via the aryl hydrocarbon receptor (AHR) 52–54 , which is expressed in most tissues, including those affected in uremia such as the liver, intestine and kidney 55, 56 . Kynurenate can also activate the orphan G-couple protein receptor, GPR35 57 , which is largely expressed in tissues affected in uremia, such as the gut and CNS 58, 59 . CMPF, on the other hand, has been implicated in a glucose sensing mechanism involving OAT3, which is expressed in the pancreas (among other non-renal tissues), leading to altered metabolism 32 .…”

Section: Discussionmentioning

confidence: 99%

Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes

Bush

Nigám

2017

Sci Rep

173

176

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In vitro data indicates that the kidney proximal tubule (PT) transporters of uremic toxins and solutes (e.g., indoxyl sulfate, p-cresol sulfate, kynurenine, creatinine, urate) include two “drug” transporters of the organic anion transporter (OAT) family: OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Here, we have examined new and prior metabolomics data from the Oat1KO and Oat3KO, as well as newly obtained metabolomics data from a “chemical double” knockout (Oat3KO plus probenecid). This gives a picture of the in vivo roles of OAT1 and OAT3 in the regulation of the uremic solutes and supports the centrality of these “drug” transporters in independently and synergistically regulating uremic metabolism. We demonstrate a key in vivo role for OAT1 and/or OAT3 in the handling of over 35 uremic toxins and solutes, including those derived from the gut microbiome (e.g., CMPF, phenylsulfate, indole-3-acetic acid). Although it is not clear whether trimethylamine-N-oxide (TMAO) is directly transported, the Oat3KO had elevated plasma levels of TMAO, which is associated with cardiovascular morbidity in chronic kidney disease (CKD). As described in the Remote Sensing and Signaling (RSS) Hypothesis, many of these molecules are involved in interorgan and interorganismal communication, suggesting that uremia is, at least in part, a disorder of RSS.

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“…Gpr26 is an orphan G-protein coupled receptor that is coupled to G s and for which an endogenous ligand is not known (Khan and He, 2017). Studies with Gpr26 knockout mice have implicated this receptor in anxiety, depression-like behaviors and obesity, but no known role in pain is known (Zhang et al, 2011).…”

Section: G-protein Coupled Receptorsmentioning

confidence: 99%

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Chamessian

Young

Qadri

et al. 2017

Preprint

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The spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different . CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/215657 doi: bioRxiv preprint first posted online Nov. 8, 2017; and Gpr26). Taken together, our study unveils a comprehensive transcriptional signature for SST neurons, highlights promising candidate genes for future analgesic development, and establishes a flexible method for transcriptional profiling of any spinal cord cell type.

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Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors

Cited by 43 publications

References 303 publications

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes

Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn

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