Biology:Neuropeptide S receptor
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The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins[1] which binds neuropeptide S (NPS).[2] It was formerly an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Mutations in this gene have also been associated with this disease.[3]
Clinical significance
In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic-like effects.[4][5]
In addition, mututations in NPSR have been linked to a susceptibility to asthma (rs3249801, A107I).[6] Hence NPSR has also been called GPRA (G protein-coupled receptor for asthma susceptibility). Activation of NPSR in the airway epithelium has a number of effects including upregulation of matrix metalloproteinases which are involved in the pathogenesis of asthma.[7] It has been shown that activation of NPSR by NPS affects both gastrointestinal motility and mucosal permeability simultaneously. Aberrant signaling and upregulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions.[8]
The very rare NPSR mutation Y206H, which makes the receptor more sensitive to NPS, is found in human families that need less sleep time than normal ones. It has similar effects in transgenic mice, making them resistant to memory impairment caused by lack of sleep.[9]
References
- ↑ "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America 100 (8): 4903–8. Apr 2003. doi:10.1073/pnas.0230374100. PMID 12679517. Bibcode: 2003PNAS..100.4903V.
- ↑ "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology 33 (3): 262–70. Sep 2005. doi:10.1165/rcmb.2004-0405OC. PMID 15947423.
- ↑ "Entrez Gene: NPSR1 neuropeptide S receptor 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=387129.
- ↑ "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron 43 (4): 487–97. Aug 2004. doi:10.1016/j.neuron.2004.08.005. PMID 15312648.
- ↑ "Neuropeptide S: a novel modulator of stress and arousal". Stress 10 (3): 221–6. Aug 2007. doi:10.1080/10253890701248673. PMID 17613937.
- ↑ "Characterization of a common susceptibility locus for asthma-related traits". Science 304 (5668): 300–4. Apr 2004. doi:10.1126/science.1090010. PMID 15073379. Bibcode: 2004Sci...304..300L.
- ↑ "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics 15 (19): 2923–35. Oct 2006. doi:10.1093/hmg/ddl234. PMID 16926187.
- ↑ "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol 309 (9): G625-34. Oct 2015. doi:10.1152/ajpgi.00104.2015. PMID 26206857.
- ↑ "Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation". Science Translational Medicine 11 (514): eaax2014. 16 October 2019. doi:10.1126/scitranslmed.aax2014. PMID 31619542. PMC 7587149. https://www.gwern.net/docs/genetics/heritable/2019-xing.pdf.
Further reading
- "A review of asthma genetics: gene expression studies and recent candidates". Journal of Applied Genetics 46 (1): 93–104. 2005. PMID 15741670.
- "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America 100 (8): 4903–8. Apr 2003. doi:10.1073/pnas.0230374100. PMID 12679517. Bibcode: 2003PNAS..100.4903V.
- "Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach". Proceedings of the National Academy of Sciences of the United States of America 101 (6): 1508–13. Feb 2004. doi:10.1073/pnas.0308250100. PMID 14757815. Bibcode: 2004PNAS..101.1508G.
- "Characterization of a common susceptibility locus for asthma-related traits". Science 304 (5668): 300–4. Apr 2004. doi:10.1126/science.1090010. PMID 15073379. Bibcode: 2004Sci...304..300L.
- "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron 43 (4): 487–97. Aug 2004. doi:10.1016/j.neuron.2004.08.005. PMID 15312648.
- "Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma". American Journal of Respiratory and Critical Care Medicine 171 (10): 1089–95. May 2005. doi:10.1164/rccm.200410-1317OC. PMID 15710598.
- "G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population". American Journal of Respiratory and Critical Care Medicine 171 (12): 1358–62. Jun 2005. doi:10.1164/rccm.200410-1312OC. PMID 15764725.
- "Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship". Biochimica et Biophysica Acta (BBA) - General Subjects 1722 (3): 235–46. Apr 2005. doi:10.1016/j.bbagen.2004.12.001. PMID 15777626.
- "Confirmation of GPRA: a putative drug target for asthma". American Journal of Respiratory and Critical Care Medicine 171 (12): 1323–4. Jun 2005. doi:10.1164/rccm.2503006. PMID 15941840.
- "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology 33 (3): 262–70. Sep 2005. doi:10.1165/rcmb.2004-0405OC. PMID 15947423.
- "Lack of association of the G protein-coupled receptor for asthma susceptibility gene with atopic dermatitis". The Journal of Allergy and Clinical Immunology 116 (1): 220–1. Jul 2005. doi:10.1016/j.jaci.2005.03.002. PMID 15990798.
- "Absence of association between asthma and high serum immunoglobulin E associated GPRA haplotypes and adult atopic dermatitis". The Journal of Investigative Dermatology 125 (2): 399–401. Aug 2005. doi:10.1111/j.0022-202X.2005.23828.x. PMID 16098057.
- "G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population". The Journal of Allergy and Clinical Immunology 117 (3): 612–7. Mar 2006. doi:10.1016/j.jaci.2005.11.045. PMID 16522461.
- "Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I". The Journal of Biological Chemistry 281 (34): 24704–12. Aug 2006. doi:10.1074/jbc.M603691200. PMID 16790440.
- "Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease". American Journal of Physiology. Lung Cellular and Molecular Physiology 291 (5): L1005-17. Nov 2006. doi:10.1152/ajplung.00174.2006. PMID 16829631.
- "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics 15 (19): 2923–35. Oct 2006. doi:10.1093/hmg/ddl234. PMID 16926187.
- "G protein-coupled receptor for asthma susceptibility associates with respiratory distress syndrome". Annals of Medicine 38 (5): 357–66. 2007. doi:10.1080/07853890600756453. PMID 16938805.
External links
- "Neuropeptide S Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1324.
- NPSR1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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