Disease relevance of NPSR1

• Absence of association between asthma and high serum immunoglobulin E associated GPRA haplotypes and adult atopic dermatitis [1].
• However, we report here that the development of allergic lung disease in GPRA-deficient mice is unaltered [2].
• Clinicians identifying severe thrombocytopenia after GPRA exposure are encouraged to report these events, following national and institutional guidelines [3].
• Factor G pathway reactive activity (GPRA) after surgery for abdominal aortic aneurysm [4].

High impact information on NPSR1

• The NPSR mRNA is widely distributed in the brain, including the amygdala and the midline thalamic nuclei [5].
• The engineered construct contained vasopressin V1a receptor with all three intracellular loops and C terminus replaced by those of VRR1 [6].
• The results show that GPR154 is upregulated in macrophages after antigen challenge and that NPS is capable of inducing phagocytosis of unopsonized bacteria [7].
• The expression of GPR154 in leukocytes was further confirmed by immunoblotting experiments and immunohistochemical staining of human sputum samples [7].
• In human blood and sputum cells, monocyte/macrophages and eosinophils were identified as GPR154-positive cells [7].

Biological context of NPSR1

• The NPS-NPSR receptor system regulates important biological functions such as sleeping/wakening, locomotion, anxiety, and food intake [8].
• Multiple hypothalamic nuclei, including the dorsomedial and the ventromedial hypothalamic nucleus and the posterior arcuate nucleus, express high levels of NPSR mRNA, indicating that NPS may regulate energy homeostasis [9].
• Notably, this inhibition is absent in the asthma-linked N107I variant of NPSR, suggesting that residue 107 interacts with the aforementioned regulatory region of NPS [10].
• One such single nucleotide polymorphism leads to the missense mutation N107I, which results in an increase in the potency of NPS for NPSR [10].
• To gain insight into structure-function relationships within NPS and NPSR, we first carried out a limited structural characterization of NPS and subjected the peptide to extensive mutagenesis studies [10].

Anatomical context of NPSR1

• Here, we characterized the mRNA expression of NPS and GPR154 by using real-time RT-PCR in fractionated human blood cells and in peripheral blood mononuclear cells (PBMCs) with monocyte or T cell activation [7].
• In the lung tissue samples and in the BAL fluid of OVA-challenged mice, GPR154 expression was upregulated in alveolar macrophages in comparison to controls [7].
• NPSR mRNA is expressed in several regions mediating anxiety responses, including the amygdaloid complex and the paraventricular hypothalamic nucleus [9].
• In addition, NPSR mRNA is strongly expressed in major output and input regions of hippocampus, including the parahippocampal regions, the lateral entorhinal cortex, and the retrosplenial agranular cortex [9].
• NPSR mRNA is also found in multiple key regions of sleep neurocircuitries, such as the thalamus, the hypothalamus, and the preoptic region [9].

Associations of NPSR1 with chemical compounds

• Here, we examined the effect of acute and chronic caffeine treatment on the expression of neuropeptide S and its receptor (NPS-R) in the hypothalamus and brainstem of rats by using real-time PCR [11].
• OBJECTIVE: To test the association between GPR154 gene polymorphisms and airway responsiveness to methacholine in a Chinese population [12].

Other interactions of NPSR1

• Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses [7].
• A 70-kb haplotype block in the G protein-coupled receptor for asthma susceptibility gene (GPR154; alias GPRA) on chromosome 7p was recently identified to influence susceptibility to asthma and elevated total serum IgE levels in adults [13].
• RATIONALE: Recently, a new asthma susceptibility gene, GPRA (G-protein-related receptor for asthma), has been identified by positional cloning [14].

Analytical, diagnostic and therapeutic context of NPSR1

• Additionally, we characterized the expression of GPR154 in the lung tissue samples and in the bronchoalveolar lavage (BAL) fluid of OVA sensitized and challenged BALB/c mice [7].
• OBJECTIVE: In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed [14].
• Additionally, we measured phosphokinase (CPK) and GPRA levels in the muscle of 10 patients during abdominal aortic aneurysm surgery and 6 during open laparotomy for other causes [4].

References