Theneuropeptide S receptor (NPSR) is a member of theG-protein coupled receptor superfamily ofintegral membrane proteins[5] which bindsneuropeptide S (NPS).[6] It was formerly anorphan 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 withasthma. 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.[7]
In addition, mututations in NPSR have been linked to a susceptibility toasthma (rs3249801, A107I).[10] Hence NPSR has also been calledGPRA (G protein-coupled receptor for asthma susceptibility). Activation of NPSR in the airwayepithelium has a number of effects including upregulation ofmatrix metalloproteinases which are involved in thepathogenesis of asthma.[11] 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.[12]
The very rare NPSR mutation Y206H, which makes the receptor more sensitive to NPS, may causefamilial natural short sleep.[13] This finding has not been investigated in animal models, and is sufficiently rare that abiobank study was unable to find other carriers to attempt a replication of the association with sleep duration.[14]
^Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, et al. (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.
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.
Melén E, Bruce S, Doekes G, Kabesch M, Laitinen T, Lauener R, et al. (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, et al. (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 (BBA) - General Subjects.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, et al. (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, et al. (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.hdl:11573/114973.PMID15990798.
Allen IC, Pace AJ, Jania LA, Ledford JG, Latour AM, Snouwaert JN, et al. (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.S2CID5888233.
Pulkkinen V, Haataja R, Hannelius U, Helve O, Pitkänen OM, Karikoski R, et al. (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.S2CID10090669.
"Neuropeptide S Receptor".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2016-02-06. Retrieved2007-11-03.
