GI functions of GPR39: novel biology

Depoortere, Inge

doi:10.1016/j.coph.2012.07.019

Cited by 40 publications

(19 citation statements)

References 59 publications

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“…In this study, the GPCR with the highest intestine spatial regulation (upregulated in the AI-MI) was GPR39 . This is an orphan receptor that belongs to the ghrelin/motilin receptor subfamily, and it is emerging as an important regulator of gastrointestinal motility and secretion (Depoortere, 2012). Two forms of GPR39 have been characterized in black sea bream ( Acanthopagrus schlegeli ), and intestinal expression of sbGPR39-1a was found to decrease significantly during food deprivation (Zhang et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Reveals Functional Specialization along the Intestinal Tract of a Carnivorous Teleostean Fish (Dicentrarchus labrax)

2016

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High-quality sequencing reads from the intestine of European sea bass were assembled, annotated by similarity against protein reference databases and combined with nucleotide sequences from public and private databases. After redundancy filtering, 24,906 non-redundant annotated sequences encoding 15,367 different gene descriptions were obtained. These annotated sequences were used to design a custom, high-density oligo-microarray (8 × 15 K) for the transcriptomic profiling of anterior (AI), middle (MI), and posterior (PI) intestinal segments. Similar molecular signatures were found for AI and MI segments, which were combined in a single group (AI-MI) whereas the PI outstood separately, with more than 1900 differentially expressed genes with a fold-change cutoff of 2. Functional analysis revealed that molecular and cellular functions related to feed digestion and nutrient absorption and transport were over-represented in AI-MI segments. By contrast, the initiation and establishment of immune defense mechanisms became especially relevant in PI, although the microarray expression profiling validated by qPCR indicated that these functional changes are gradual from anterior to posterior intestinal segments. This functional divergence occurred in association with spatial transcriptional changes in nutrient transporters and the mucosal chemosensing system via G protein-coupled receptors. These findings contribute to identify key indicators of gut functions and to compare different fish feeding strategies and immune defense mechanisms acquired along the evolution of teleosts.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Reveals Functional Specialization along the Intestinal Tract of a Carnivorous Teleostean Fish (Dicentrarchus labrax)

2016

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“…Activation of the GPR39 triggers diverse neuronal pathways ( Holst et al, 2004 , 2007 ; Popovics and Stewart, 2011 ) that may be involved in neuroprotection ( Depoortere, 2012 ). Zinc stimulates GPR39 activity, which activates the Gα s , Gα q , and Gα 12/13 pathways ( Holst et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

GPR39 (Zinc Receptor) Knockout Mice Exhibit Depression-Like Behavior and CREB/BDNF Down-Regulation in the Hippocampus

Młyniec

Budziszewska

Holst

et al. 2015

International Journal of Neuropsychopharmacology

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Background:Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors.Methods:In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspension test, and light/dark test. We also investigated whether lack of GPR39 would change levels of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and frontal cortex of GPR39 knockout mice subjected to the forced swim test, as measured by Western-blot analysis.Results:In this study, GPR39 knockout mice showed an increased immobility time in both the forced swim test and tail suspension test, indicating depressive-like behavior and displayed anxiety-like phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus, but not in the frontal cortex, which indicates region specificity for the impaired CREB/BDNF pathway (which is important in antidepressant response) in the absence of GPR39. There were no changes in TrkB protein in either structure. In the present study, we also investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex.Conclusions:There were no changes in the GPR39 knockout mice in comparison with the wild-type control mice, which does not support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The results of this study indicate the involvement of the GPR39 Zn2+-sensing receptor in the pathophysiology of depression with component of anxiety.

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“…Originally, it was thought that obestatin was the endogenous ligand for GPR39 and could inhibit food intake and gastric motility, functions that could counteract the effect of ghrelin [54] . However, several independent groups could not confirm these findings and identified Zn 2+ as a physiological agonist of GPR39 [55] . To activate its only known receptor, ghrelin requires the attachment of a fatty acid side-chain (preferably C8 or C10) to its serine 3 residue, a rare post-translational modification (acylation) that is achieved by the ghrelin O -acyl-transferase (GOAT), a member of the membrane-bound O -acyltransferase (MBOAT) family [56,57] ( Figure 2 ).…”

Section: Regulation Of Ghrelin Acylationmentioning

confidence: 94%

Ghrelin

Müller

Nogueiras

Andermann

et al. 2015

Molecular Metabolism

897

654

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BackgroundThe gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.Scope of reviewIn this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery.Major conclusionsIn recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

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GI functions of GPR39: novel biology

Cited by 40 publications

References 59 publications

Gene Expression Profiling Reveals Functional Specialization along the Intestinal Tract of a Carnivorous Teleostean Fish (Dicentrarchus labrax)

Gene Expression Profiling Reveals Functional Specialization along the Intestinal Tract of a Carnivorous Teleostean Fish (Dicentrarchus labrax)

GPR39 (Zinc Receptor) Knockout Mice Exhibit Depression-Like Behavior and CREB/BDNF Down-Regulation in the Hippocampus

Ghrelin

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