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]
In addition, mututations in NPSR have been linked to a susceptibility to asthma.[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]
↑Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, Laitinen LA, Kere J, Laitinen T (Sep 2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID15947423.
↑Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97. doi:10.1016/j.neuron.2004.08.005. PMID15312648.
↑Okamura N, Reinscheid RK (Aug 2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress. 10 (3): 221–6. doi:10.1080/10253890701248673. PMID17613937.
↑Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, Mäkelä S, Rehn M, Pirskanen A, Rautanen A, Zucchelli M, Gullstén H, Leino M, Alenius H, Petäys T, Haahtela T, Laitinen A, Laprise C, Hudson TJ, Laitinen LA, Kere J (Apr 2004). "Characterization of a common susceptibility locus for asthma-related traits". Science. 304 (5668): 300–4. doi:10.1126/science.1090010. PMID15073379.
↑Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytilä P, Pirskanen A, Rehn M, Laitinen T, Laitinen LA, Haahtela T, Saarialho-Kere U, Laitinen A, Kere J (Oct 2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics. 15 (19): 2923–35. doi:10.1093/hmg/ddl234. PMID16926187.
↑Wan Saudi WS, Halim MA, Rudholm-Feldreich T, Gillberg L, Rosenqvist E, Tengholm A, Sundbom M, Karlbom U, Näslund E, Webb DL, Sjöblom M, Hellström PM (Oct 2015). "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol. 309 (9): G625–34. doi:10.1152/ajpgi.00104.2015. PMID26206857.
Further reading
Malerba G, Pignatti PF (2005). "A review of asthma genetics: gene expression studies and recent candidates". Journal of Applied Genetics. 46 (1): 93–104. PMID15741670.
Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, Mäkelä S, Rehn M, Pirskanen A, Rautanen A, Zucchelli M, Gullstén H, Leino M, Alenius H, Petäys T, Haahtela T, Laitinen A, Laprise C, Hudson TJ, Laitinen LA, Kere J (Apr 2004). "Characterization of a common susceptibility locus for asthma-related traits". Science. 304 (5668): 300–4. doi:10.1126/science.1090010. PMID15073379.
Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97. doi:10.1016/j.neuron.2004.08.005. PMID15312648.
Melén E, Bruce S, Doekes G, Kabesch M, Laitinen T, Lauener R, Lindgren CM, Riedler J, Scheynius A, van Hage-Hamsten M, Kere J, Pershagen G, Wickman M, Nyberg F (May 2005). "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. doi:10.1164/rccm.200410-1317OC. PMID15710598.
Kormann MS, Carr D, Klopp N, Illig T, Leupold W, Fritzsch C, Weiland SK, von Mutius E, Kabesch M (Jun 2005). "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. doi:10.1164/rccm.200410-1312OC. PMID15764725.
Gloriam DE, Schiöth HB, Fredriksson R (Apr 2005). "Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship". Biochimica et Biophysica Acta. 1722 (3): 235–46. doi:10.1016/j.bbagen.2004.12.001. PMID15777626.
Postma DS, Koppelman GH (Jun 2005). "Confirmation of GPRA: a putative drug target for asthma". American Journal of Respiratory and Critical Care Medicine. 171 (12): 1323–4. doi:10.1164/rccm.2503006. PMID15941840.
Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, Laitinen LA, Kere J, Laitinen T (Sep 2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID15947423.
Söderhäll C, Marenholz I, Nickel R, Grüber C, Kehrt R, Rohde K, Griffioen RW, Meglio P, Tarani L, Gustafsson D, Hoffmann U, Gerstner B, Müller S, Wahn U, Lee YA (Jul 2005). "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. doi:10.1016/j.jaci.2005.03.002. PMID15990798.
Veal CD, Reynolds NJ, Meggitt SJ, Allen MH, Lindgren CM, Kere J, Trembath RC, Barker JN (Aug 2005). "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. doi:10.1111/j.0022-202X.2005.23828.x. PMID16098057.
Feng Y, Hong X, Wang L, Jiang S, Chen C, Wang B, Yang J, Fang Z, Zang T, Xu X, Xu X (Mar 2006). "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. doi:10.1016/j.jaci.2005.11.045. PMID16522461.
Bernier V, Stocco R, Bogusky MJ, Joyce JG, Parachoniak C, Grenier K, Arget M, Mathieu MC, O'Neill GP, Slipetz D, Crackower MA, Tan CM, Therien AG (Aug 2006). "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. doi:10.1074/jbc.M603691200. PMID16790440.
Allen IC, Pace AJ, Jania LA, Ledford JG, Latour AM, Snouwaert JN, Bernier V, Stocco R, Therien AG, Koller BH (Nov 2006). "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. doi:10.1152/ajplung.00174.2006. PMID16829631.
Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytilä P, Pirskanen A, Rehn M, Laitinen T, Laitinen LA, Haahtela T, Saarialho-Kere U, Laitinen A, Kere J (Oct 2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics. 15 (19): 2923–35. doi:10.1093/hmg/ddl234. PMID16926187.
Pulkkinen V, Haataja R, Hannelius U, Helve O, Pitkänen OM, Karikoski R, Rehn M, Marttila R, Lindgren CM, Hästbacka J, Andersson S, Kere J, Hallman M, Laitinen T (2007). "G protein-coupled receptor for asthma susceptibility associates with respiratory distress syndrome". Annals of Medicine. 38 (5): 357–66. doi:10.1080/07853890600756453. PMID16938805.
External links
"Neuropeptide S Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.