Abstract
Neuropeptide S (NPS) is one of the most recent examples of a neurotransmitter identified by the orphan receptor strategy. Impressive progress has been made in the short time since its identification to determine physiological functions modulated by NPS. The anatomical distribution of NPS and its receptor, NPSR, suggests possible functions in the regulation of vigilance states and modulation of emotional behaviors. Early studies provided evidence that NPS induces behavioral arousal and promotes wakefulness by suppressing all stages of sleep. NPS was also found to produce anxiolytic-like effects in behavioral paradigms that measure fear or responses to novelty. Recent studies have demonstrated that NPS can modulate energy and endocrine homeostasis. Differential regulation of NPS and NPSR transcripts was observed after caffeine or nicotine treatment, indicating complex interactions with adenosine and cholinergic systems. NPS has been found co-localized with other excitatory transmitters such as glutamate, acetylcholine, or corticotropine-releasing factor. Activation of NPSR triggers mobilization of intracellular Ca2+ and stimulation of cAMP synthesis, therefore increasing cellular excitability. A functional polymorphism in NPSR has been identified that produces a gain-of-function phenotype by increasing agonist potency up to tenfold. Finally, a gender-specific association of this NPSR polymorphism with panic disorder was found in male patients, indicating that the NPS system might be involved in modulating anxiety responses in humans. Further studies about interactions of the NPS system with other transmitter systems might help to discover additional functions of NPS and define its role within complex neural networks.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
References
Allen IC, Pace AJ, Jania LA, Ledford JG, Latour AM, Snouwaert JN, Bernier V, Stocco R, Therien AG, Koller BH (2006) Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease. Am J Physiol Lung Cell Mol Physiol 291:L1005–L1017
Beck B, Fernette B, Stricker-Krongrad A (2005) Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in rats. Biochem Biophys Res Commun 332:859–865
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 (2006) Structure–function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I. J Biol Chem 281:24704–24712
Bourin M, Malinge M, Guitton B (1995) Provocative agents in panic disorder. Therapie 50:301–306
Chaouloff F, Durand M, Mormede P (1997) Anxiety- and activity-related effects of diazepam and chlordiazepoxide in the rat light/dark and dark/light tests. Behav Brain Res 85:27–35
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451
Crowe RR, Goedken R, Samuelson S, Wilson R, Nelson J, Noyes R Jr (2001) Genomewide survey of panic disorder. Am J Med Genet 105:105–109
Feng Y, Hong X, Wang L, Jiang S, Chen C, Wang B, Yang J, Fang Z, Zang T, Xu X, Xu X (2006) G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population. J Allergy Clin Immunol 117:612–617
Gupte J, Cutler G, Chen JL, Tian H (2004) Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach. Proc Natl Acad Sci USA 101:1508–1513
Haefely WE (1989) Pharmacology of the benzodiazepine receptor. Eur Arch Psychiatry Neurol Sci 238:294–301
Hascoet M, Bourin M (1998) A new approach to the light/dark test procedure in mice. Pharmacol Biochem Behav 60:645–653
Immervoll T, Loesgen S, Dutsch G, Gohlke H, Herbon N, Klugbauer S, Dempfle A, Bickeboller H, Becker-Follmann J, Ruschendorf F, Saar K, Reis A, Wichmann HE, Wjst M (2001) Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes. Hum Mutat 18:327–336
Jones BE (2003) Arousal systems. Front Biosci 8:438–451
Knowles JA, Fyer AJ, Vieland VJ, Weissman MM, Hodge SE, Heiman GA, Haghighi F, de Jesus GM, Rassnick H, Preud'homme-Rivelli X, Austin T, Cunjak J, Mick S, Fine LD, Woodley KA, Das K, Maier W, Adams PB, Freimer NB, Klein DF, Gilliam TC (1998) Results of a genome-wide genetic screen for panic disorder. Am J Med Genet 81:139–147
Koob GF, Greenwell TN (2004) Neuropeptide S: a novel activating anxiolytic? Neuron 43:441–442
Kormann MS, Carr D, Klopp N, Illig T, Leupold W, Fritzsch C, Weiland SK, von Mutius E, Kabesch M (2005) G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population. Am J Respir Crit Care Med 171:1358–1362
Lage R, Dieguez C, Lopez M (2006) Caffeine treatment regulates neuropeptide S system expression in the rat brain. Neurosci Lett 410:47–51
Lage R, Gonzalez CR, Dieguez C, Lopez M (2007) Nicotine treatment regulates neuropeptide S system expression in the rat brain. Neurotoxicology 28(6):1129–1135
Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, Makela S, Rehn M, Pirskanen A, Rautanen A, Zucchelli M, Gullsten H, Leino M, Alenius H, Petays T, Haahtela T, Laitinen A, Laprise C, Hudson TJ, Laitinen LA, Kere J (2004) Characterization of a common susceptibility locus for asthma-related traits. Science 304:300–304
Lee FJ, Xue S, Pei L, Vukusic B, Chery N, Wang Y, Wang YT, Niznik HB, Yu XM, Liu F (2002) Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell 111:219–230
Leonard SK, Malberg JE, Schechter LE, Luo B, Platt B, Rosenzweig-Lipson S, Ring RH (2005) Behavioral effects of neuropeptide S in mouse models of anxiety and depression. SFN 2005 abstract viewer for 35th annual meeting. Society for Neuroscience, Washington, DC, Program no. 889.14. Available online at http://sfn.scholarone.com/itin2005/index.html ; last visited 7 Dec 2007
Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98:365–376
Lin SH, Arai AC, Wang Z, Nothacker HP, Civelli O (2001) The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering. Mol Pharmacol 60:916–923
Malerba G, Lindgren CM, Xumerle L, Kiviluoma P, Trabetti E, Laitinen T, Galavotti R, Pescollderungg L, Boner AL, Kere J, Pignatti PF (2007) Chromosome 7p linkage and GPR154 gene association in Italian families with allergic asthma. Clin Exp Allergy 37:83–89
Melen 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 (2005) PARSIFAL Genetics Study Group Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma. Am J Respir Crit Care Med 171:1089–1095
Niimi M (2006) Centrally administered neuropeptide S activates orexin-containing neurons in the hypothalamus and stimulates feeding in rats. Endocrine 30:75–79
Okamura N, Reinscheid RK (2007) Neuropeptide S: a novel modulator or stress and arousal. Stress 10:221–226
Okamura N, Hashimoto K, Iyo M, Shimizu E, Dempfle A, Friedel S, Reinscheid RK (2007) Gender-specific association of a functional coding polymorphism in the neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder. Prog Neuropharmacol Biol Psychiatry 31(7):1444–1448
Paine TA, Jackman SL, Olmstead MC (2002) Cocaine-induced anxiety: alleviation by diazepam, but not buspirone, dimenhydrinate or diphenhydramine. Behav Pharmacol 13:511–523
Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3rd edn. Academic, New York
Reinscheid RK, Xu YL (2005) Neuropeptide S as a novel arousal promoting peptide transmitter. FEBS J 272:5689–5693
Reinscheid RK, Xu YL, Okamura N, Zeng J, Chung S, Pai R, Wang Z, Civelli O (2005) Pharmacological characterization of human and murine neuropeptide S receptor variants. J Pharmacol Exp Ther 315:1338–1345
Reinscheid RK (2007) Phylogenetic appearance of neuropeptide S precursor proteins in tetrapods. Peptides 28:830–837
Roth AL, Marzola E, Rizzi A, Arduin M, Trapella C, Corti C, Vergura R, Martinelli P, Salvadori S, Regoli D, Corsi M, Cavanni P, Calo G, Guerrini R (2006) Structure–activity studies on neuropeptide S: identification of the amino acid residues crucial for receptor activation. J Biol Chem 281:20809–20816
Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585
Sakurai T (2006) Roles of orexins and orexin receptors in central regulation of feeding behavior and energy homeostasis. CNS Neurol Disord Drug Targets 5:313–325
Saper CB (2006) Staying awake for dinner: hypothalamic integration of sleep, feeding, and circadian rhythms. Prog Brain Res 153:243–252
Sato S, Shintani Y, Miyajima N, Yoshimura K (2002) Novel G protein-coupled receptor protein and DNA thereof. WO Patent application 02/31145 A1
Shin HD, Park KS, Park CS (2004) Lack of association of GPRA (G protein-coupled receptor for asthma susceptibility) haplotypes with high serum IgE or asthma in a Korean population. J Allergy Clin Immunol 114:1226–1227
Smith KL, Patterson M, Dhillo WS, Patel SR, Semjonous NM, Gardiner JV, Ghatei MA, Bloom SR (2006) Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits food intake. Endocrinology 147:3510–3518
Söderhäll C, Marenholz I, Nickel R, Grüber C, Kehrt R, Rohde K, Griffioen R, Meglio P, Tarani L, Gustafsson D (2005) Lack of association of the G protein coupled receptor for asthma susceptibility gene with atopic dermatitis. J Allergy Clin Immunol 116:220–221
van der Werf YD, Witter MP, Groenewegen HJ (2002) The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness. Brain Res Rev 39:107–140
Veal CD, Reynolds NJ, Meggitt SJ, Allen MH, Lindgren CM, Kere J, Trembath RC, Barker JN (2005) Absence of association between asthma and high serum immunoglobulin E associated GPRA haplotypes and adult atopic dermatitis. J Invest Dermatol 125:399–401
Vettor R, Fabris R, Pagano C, Federspil G (2002) Neuroendocrine regulation of eating behavior. J Endocrinol Invest 25:836–854
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 (2004) Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron 43:487–497
Xu YL, Gall CM, Jackson VR, Civelli O, Reinscheid RK (2007) Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol 500:84–102
Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T (2003) Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38:701–713
Author information
Authors and Affiliations
Corresponding author
Editor information
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Reinscheid, R.K. (2008). Neuropeptide S: Anatomy, Pharmacology, Genetics and Physiological Functions. In: Civelli, O., Zhou, QY. (eds) Orphan G Protein-Coupled Receptors and Novel Neuropeptides. Results and Problems in Cell Differentiation, vol 46. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2007_051
Download citation
DOI: https://doi.org/10.1007/400_2007_051
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-78350-3
Online ISBN: 978-3-540-78351-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)