The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins[5] which binds neuropeptide S (NPS).[6] 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.[7]
In addition, mututations in NPSR have been linked to a susceptibility to asthma (rs3249801, A107I).[10] 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.[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 cause familial natural short sleep.[13] This finding has not been investigated in animal models, and is sufficiently rare that a biobank 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.
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 from the original on 2016-02-06. Retrieved 2007-11-03.
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