neuropeptide receptors


Summary: Cell surface receptors that bind specific neuropeptides with high affinity and trigger intracellular changes influencing the behavior of cells. Many neuropeptides are also hormones outside of the nervous system.

Top Publications

  1. Akbari E, Motamedi F, Naghdi N, Noorbakhshnia M. The effect of antagonization of orexin 1 receptors in CA1 and dentate gyrus regions on memory processing in passive avoidance task. Behav Brain Res. 2008;187:172-7 pubmed
    ..However, SB-334867-A administration into DG region impaired acquisition and consolidation but not PA memory retrieval. Therefore, it seems that endogenous orexins play an important role in learning and memory in the rat through OX1Rs. ..
  2. El Firar A, Voisin T, Rouyer Fessard C, Ostuni M, Couvineau A, Laburthe M. Discovery of a functional immunoreceptor tyrosine-based switch motif in a 7-transmembrane-spanning receptor: role in the orexin receptor OX1R-driven apoptosis. FASEB J. 2009;23:4069-80 pubmed publisher
    ..These data represent the first evidence for a functional role of an ITSM in a 7-transmembrane-spanning receptor. ..
  3. Matsuki T, Nomiyama M, Takahira H, Hirashima N, Kunita S, Takahashi S, et al. Selective loss of GABA(B) receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc Natl Acad Sci U S A. 2009;106:4459-64 pubmed publisher
    ..Thus, GABA(B) receptors on orexin neurons are crucial in the appropriate control of the orexinergic tone through sleep/wake states, thereby stabilizing the state switching mechanisms. ..
  4. Hauser F, Williamson M, Cazzamali G, Grimmelikhuijzen C. Identifying neuropeptide and protein hormone receptors in Drosophila melanogaster by exploiting genomic data. Brief Funct Genomic Proteomic. 2006;4:321-30 pubmed
    ..In this review, we will give an update about the current knowledge of all Drosophila neuropeptide and protein hormone receptors, and discuss their phylogenetic relationships. ..
  5. Lee K, Kwon O, Lee J, Kwon K, Min K, Jung S, et al. Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat Cell Biol. 2008;10:468-75 pubmed publisher
    ..Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK-mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan. ..
  6. Zhao L, Yano T, Osuga Y, Nakagawa S, Oishi H, Wada Hiraike O, et al. Cellular mechanisms of growth inhibition of human endometrial cancer cell line by an antagonist of growth hormone-releasing hormone. Int J Oncol. 2008;32:593-601 pubmed
  7. Bisetti A, Cvetkovic V, Serafin M, Bayer L, Machard D, Jones B, et al. Excitatory action of hypocretin/orexin on neurons of the central medial amygdala. Neuroscience. 2006;142:999-1004 pubmed
    ..These results suggest that the hcrt/orx system can act through the amygdala to augment arousal and evoke the autonomic and behavioral responses associated with fear, stress or emotion. ..
  8. Cho H, Acharjee S, Moon M, Oh D, Vaudry H, Kwon H, et al. Molecular evolution of neuropeptide receptors with regard to maintaining high affinity to their authentic ligands. Gen Comp Endocrinol. 2007;153:98-107 pubmed
    ..Such analysis provides clues for understanding how GPCRs maintain high affinity to their authentic ligands. ..
  9. Adamantidis A, Zhang F, Aravanis A, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450:420-4 pubmed
    ..This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology. ..

More Information


  1. Akbari E, Naghdi N, Motamedi F. The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze. Peptides. 2007;28:650-6 pubmed
    ..Therefore, it seems that endogenous orexin-A and orexin-B, through DG OX1Rs, play an important role in spatial learning and memory in the rat. ..
  2. Millan M, Dekeyne A. Discriminative stimulus properties of the selective norepinephrine reuptake inhibitor, reboxetine, in rats: a characterization with alpha/beta-adrenoceptor subtype selective ligands, antidepressants, and antagonists at neuropeptide receptors. Int J Neuropsychopharmacol. 2007;10:579-93 pubmed
    ..The neurokinin-1 antagonist, GR205,171, mimics the interoceptive properties of reboxetine, possibly reflecting its elevation of extracellular levels of NE in corticolimbic structures. ..
  3. Tan E, Yamaguchi Y, Horwitz G, Gosgnach S, Lein E, Goulding M, et al. Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor. Neuron. 2006;51:157-70 pubmed
    ..Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective for selective, quick, and reversible silencing of mammalian neurons in vivo. ..
  4. Zitnan D, Kim Y, Zitnanova I, Roller L, Adams M. Complex steroid-peptide-receptor cascade controls insect ecdysis. Gen Comp Endocrinol. 2007;153:88-96 pubmed
    ..2) Release and interaction of Inka cell peptide hormones and multiple central neuropeptides to control consecutive phases of the ecdysis sequence. ..
  5. Lettre G, Butler J, Ardlie K, Hirschhorn J. Common genetic variation in eight genes of the GH/IGF1 axis does not contribute to adult height variation. Hum Genet. 2007;122:129-39 pubmed
  6. Ohno K, Sakurai T. Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol. 2008;29:70-87 pubmed
    ..This review discusses the mechanism by which orexins maintain sleep/wakefulness states, and how this mechanism relates to other systems that regulate emotion, reward, and energy homeostasis. ..
  7. Schally A, Varga J, Engel J. Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab. 2008;4:33-43 pubmed
    ..Further development of GHRH antagonists that are still-more potent should lead to potential therapeutic agents for various cancers. ..
  8. Matsuki T, Sakurai T. Orexins and orexin receptors: from molecules to integrative physiology. Results Probl Cell Differ. 2008;46:27-55 pubmed publisher
    ..In this chapter, we discuss the current understanding of the physiological roles of orexins in regulation of arousal, sleep/wake states, energy homeostasis, and reward systems. ..
  9. Bring D, Reno C, Renstrom P, Salo P, Hart D, Ackermann P. Joint immobilization reduces the expression of sensory neuropeptide receptors and impairs healing after tendon rupture in a rat model. J Orthop Res. 2009;27:274-80 pubmed publisher
    ..The expression of sensory neuropeptide receptors in the mobilized group exhibited a significant increase from 8 to 17 days postinjury similar to the ..
  10. Barabutis N, Tsellou E, Schally A, Kouloheri S, Kalofoutis A, Kiaris H. Stimulation of proliferation of MCF-7 breast cancer cells by a transfected splice variant of growth hormone-releasing hormone receptor. Proc Natl Acad Sci U S A. 2007;104:5575-9 pubmed
    ..Collectively, our findings show that the expression of SV1 confers oncogenic activity and provide further evidence that GHRH operates as a growth factor in breast cancer and probably other cancers as well. ..
  11. Voisin T, El Firar A, Rouyer Fessard C, Gratio V, Laburthe M. A hallmark of immunoreceptor, the tyrosine-based inhibitory motif ITIM, is present in the G protein-coupled receptor OX1R for orexins and drives apoptosis: a novel mechanism. FASEB J. 2008;22:1993-2002 pubmed publisher
    ..These data unravel a novel mechanism, whereby ITIM-expressing GPCRs may trigger apoptosis. ..
  12. Hohla F, Schally A, Szepeshazi K, Varga J, Buchholz S, Koster F, et al. Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel. Proc Natl Acad Sci U S A. 2006;103:14513-8 pubmed
  13. Näsman J, Bart G, Larsson K, Louhivuori L, Peltonen H, Akerman K. The orexin OX1 receptor regulates Ca2+ entry via diacylglycerol-activated channels in differentiated neuroblastoma cells. J Neurosci. 2006;26:10658-66 pubmed
    ..The results suggest that the OX1R activates a Ca2+ entry pathway that involves diacylglycerol-activated TRPC channels in neuronal cells. ..
  14. Tan W, Janczewski W, Yang P, Shao X, Callaway E, Feldman J. Silencing preBötzinger complex somatostatin-expressing neurons induces persistent apnea in awake rat. Nat Neurosci. 2008;11:538-40 pubmed publisher
    ..We hypothesize that breathing requires preBötC Sst neurons and that their sudden depression can lead to serious, even fatal, respiratory failure. ..
  15. Brisbare Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007;13:150-5 pubmed
    ..No signs of cataplexy were observed, in contrast to the rodent, dog or human narcolepsy syndromes. These results open new perspectives for investigating the role of endogenous orexins in sleep-wake regulation. ..
  16. Hull J, Ohnishi A, Moto K, Kawasaki Y, Kurata R, Suzuki M, et al. Cloning and characterization of the pheromone biosynthesis activating neuropeptide receptor from the silkmoth, Bombyx mori. Significance of the carboxyl terminus in receptor internalization. J Biol Chem. 2004;279:51500-7 pubmed
    ..From these results, we have concluded that the cloned receptor gene encodes the B. mori PBANR and that it is both structurally and functionally distinct from the H. zea PBANR. ..
  17. Mobarakeh J, Takahashi K, Sakurada S, Nishino S, Watanabe H, Kato M, et al. Enhanced antinociception by intracerebroventricularly and intrathecally-administered orexin A and B (hypocretin-1 and -2) in mice. Peptides. 2005;26:767-77 pubmed
    ..The present findings suggest that orexins have an antinociceptive role in at least four different types of pains, probably acting on both the brain and spinal cord. ..
  18. Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff T, Yagami K, et al. Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor. J Neurosci. 2005;25:7459-69 pubmed
    ..The evidence presented here expands our understanding of the regulation of orexin neurons and the physiological role of CCK in the CNS. ..
  19. Winsky Sommerer R, Boutrel B, de Lecea L. Stress and arousal: the corticotrophin-releasing factor/hypocretin circuitry. Mol Neurobiol. 2005;32:285-94 pubmed
  20. Fukusumi S, Fujii R, Hinuma S. Recent advances in mammalian RFamide peptides: the discovery and functional analyses of PrRP, RFRPs and QRFP. Peptides. 2006;27:1073-86 pubmed
    ..We review here the strategies employed for the identification of these peptides and examine their characteristics, tissue distribution, receptors and functions. ..
  21. Schurks M, Kurth T, Geissler I, Tessmann G, Diener H, Rosskopf D. Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene. Neurology. 2006;66:1917-9 pubmed
    ..The genotype and allele distribution varied significantly between patients and controls. Homozygous carriers of the G-allele had a twofold increase in risk for CH (OR 1.97; 95% CI 1.32 to 2.92; p = 0.0007). ..
  22. Yamanaka A, Muraki Y, Ichiki K, Tsujino N, Kilduff T, Goto K, et al. Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner. J Neurophysiol. 2006;96:284-98 pubmed
    ..The evidence presented here revealed that orexin neurons are regulated by catecholamines in a complex manner. ..
  23. Xu Y, Reinscheid R, Huitron Resendiz S, Clark S, Wang Z, Lin S, et al. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron. 2004;43:487-97 pubmed
    ..These results indicate that NPS could be a new modulator of arousal and anxiety. They also show that the LC region encompasses distinct nuclei expressing different arousal-promoting neurotransmitters. ..
  24. Rainero I, Gallone S, Valfrè W, Ferrero M, Angilella G, Rivoiro C, et al. A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache. Neurology. 2004;63:1286-8 pubmed
    ..Homozygosity for the G allele was associated with an increased disease risk (OR: 6.79, 95% CI, 2.25 to 22.99). The data suggest that the HCRTR2 gene or a linked locus significantly modulates the risk for cluster headache. ..
  25. Winsky Sommerer R, Yamanaka A, Diano S, Borok E, Roberts A, Sakurai T, et al. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci. 2004;24:11439-48 pubmed
    ..We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response. ..
  26. Ishii Y, Blundell J, Halford J, Upton N, Porter R, Johns A, et al. Anorexia and weight loss in male rats 24 h following single dose treatment with orexin-1 receptor antagonist SB-334867. Behav Brain Res. 2005;157:331-41 pubmed
  27. J rgensen L, Hauser F, Cazzamali G, Williamson M, Grimmelikhuijzen C. Molecular identification of the first SIFamide receptor. Biochem Biophys Res Commun. 2006;340:696-701 pubmed publisher
    ..This paper is the first report on the identification of a SIFamide receptor...
  28. Greenwood K, Williams T, Geary T. Nematode neuropeptide receptors and their development as anthelmintic screens. Parasitology. 2005;131 Suppl:S169-77 pubmed
    This review addresses the potential use of neuropeptide receptors for the discovery of anthelmintic agents, and particularly for the identification of non-peptide ligands...
  29. Xie X, Crowder T, Yamanaka A, Morairty S, Lewinter R, Sakurai T, et al. GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus. J Physiol. 2006;574:399-414 pubmed
  30. Baumber L, Sjöstrand C, Leone M, Harty H, Bussone G, Hillert J, et al. A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort. Neurology. 2006;66:1888-93 pubmed
    ..Cluster headache is a complex genetic disorder, with possible phenotypic and genetic heterogeneity compounding attempts at gene identification. ..
  31. Akbari E, Naghdi N, Motamedi F. Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze task. Behav Brain Res. 2006;173:47-52 pubmed
    ..This drug had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous orexins, especially orexin-A, play an important role in spatial learning and memory in the rat. ..
  32. Schürks M, Limmroth V, Geissler I, Tessmann G, Savidou I, Engelbergs J, et al. Association between migraine and the G1246A polymorphism in the hypocretin receptor 2 gene. Headache. 2007;47:1195-9 pubmed
    ..13, 2 df, P= .13; allele distribution: chi(2)= 0.9, 1 df, P= .34). Our study does not support a major contribution of the HCRTR2 G1246A polymorphism to the pathogenesis of migraine in contrast to its effects in cluster headache. ..
  33. Rostkowski A, Teppen T, Peterson D, Urban J. Cell-specific expression of neuropeptide Y Y1 receptor immunoreactivity in the rat basolateral amygdala. J Comp Neurol. 2009;517:166-76 pubmed publisher
  34. Ritchie C, Okuro M, Kanbayashi T, Nishino S. Hypocretin ligand deficiency in narcolepsy: recent basic and clinical insights. Curr Neurol Neurosci Rep. 2010;10:180-9 pubmed publisher
    ..Currently, hypocretin replacement therapy has emerged as a promising therapeutic option, and experiments using gene therapy and cell transplantation are in progress. ..
  35. Gaubert G, Bertozzi F, Kelly N, Pawlas J, Scully A, Nash N, et al. Discovery of selective nonpeptidergic neuropeptide FF2 receptor agonists. J Med Chem. 2009;52:6511-4 pubmed publisher
  36. Garczynski S, Crim J, Brown M. Characterization and expression of the short neuropeptide F receptor in the African malaria mosquito, Anopheles gambiae. Peptides. 2007;28:109-18 pubmed
    ..Membranes from female heads and thoraces exhibited prototypical high affinity binding for radiolabeled sNPF, indicating sNPFR is a bona fide endogenous receptor. ..
  37. Brzozowski T, Konturek P, Sliwowski Z, Drozdowicz D, Burnat G, Pajdo R, et al. Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglandins, sensory afferent neuropeptides and nitric oxide. Regul Pept. 2008;148:6-20 pubmed publisher
  38. Karamanolis G, Tack J. Promotility medications--now and in the future. Dig Dis. 2006;24:297-307 pubmed
  39. Johnson P, Truitt W, Fitz S, Minick P, Dietrich A, Sanghani S, et al. A key role for orexin in panic anxiety. Nat Med. 2010;16:111-5 pubmed publisher
    ..Taken together, our results suggest that the ORX system may be involved in the pathophysiology of panic anxiety and that ORX antagonists constitute a potential new treatment strategy for panic disorder. ..
  40. Taneja Bageshwar S, Strey A, Kaczmarek K, Zabrocki J, Pietrantonio P, Nachman R. Comparison of insect kinin analogs with cis-peptide bond, type VI-turn motifs identifies optimal stereochemistry for interaction with a recombinant arthropod kinin receptor from the southern cattle tick Boophilus microplus. Peptides. 2008;29:295-301 pubmed publisher
    ..These biostable analogs provide new tools for arthropod endocrinologists and potential leads in the development of selective, environmentally friendly arthropod pest control agents capable of disrupting insect kinin regulated processes. ..
  41. Sharf R, Guarnieri D, Taylor J, DiLeone R. Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitization. Brain Res. 2010;1317:24-32 pubmed publisher
    ..These data suggest that orexin action is not required for locomotor responses to acute and chronic morphine, but Ox1r signaling can influence morphine-seeking in WT animals. ..
  42. Gudermann T, Roelle S. Calcium-dependent growth regulation of small cell lung cancer cells by neuropeptides. Endocr Relat Cancer. 2006;13:1069-84 pubmed
    ..In the case of SCLC, targeting the distinct components of the Ca2+ influx pathway as well as critical Ca2+-dependent cellular effectors may be rewarding in this regard. ..
  43. Arias Carrión O, Murillo Rodriguez E. Cell transplantation: a future therapy for narcolepsy?. CNS Neurol Disord Drug Targets. 2009;8:309-14 pubmed
    ..This article reviews the current understanding of narcolepsy and discusses the opportunity to explore the potential use of transplants as a therapeutical tool in order to treat narcolepsy. ..
  44. Azizi H, Mirnajafi Zadeh J, Rohampour K, Semnanian S. Antagonism of orexin type 1 receptors in the locus coeruleus attenuates signs of naloxone-precipitated morphine withdrawal in rats. Neurosci Lett. 2010;482:255-9 pubmed publisher
    ..These results suggest that activation of OXR1 in the LC might be involved in the expression of withdrawal signs in morphine dependent rats...
  45. Garcia Tornadú I, Diaz Torga G, Risso G, Silveyra P, Cataldi N, Ramirez M, et al. Hypothalamic orexin, OX1, alphaMSH, NPY and MCRs expression in dopaminergic D2R knockout mice. Neuropeptides. 2009;43:267-74 pubmed publisher
    ..These results suggest a sexually dimorphic participation of the D2R in food intake regulation. ..
  46. Tokunaga H, Matsuura B, Dong M, Miller L, Ueda T, Furukawa S, et al. Mutational analysis of predicted intracellular loop domains of human motilin receptor. Am J Physiol Gastrointest Liver Physiol. 2008;294:G460-6 pubmed
    ..The identification of functionally important residues in the predicted cytosolic face provides strong candidates for playing roles in receptor-G protein interaction. ..
  47. Marsault E, Benakli K, Beaubien S, Saint Louis C, Deziel R, Fraser G. Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural amino acids. Bioorg Med Chem Lett. 2007;17:4187-90 pubmed
    ..These peptidomimetic macrocycles are composed of a tripeptide cyclized backbone-to-backbone with a nonpeptidic tether and bear new unnatural amino acids containing basic side chains. ..
  48. Martynska L, Polkowska J, Wolinska Witort E, Chmielowska M, Wasilewska Dziubinska E, Bik W, et al. Orexin A and its role in the regulation of the hypothalamo-pituitary axes in the rat. Reprod Biol. 2006;6 Suppl 2:29-35 pubmed
    ..Further studies are necessary to clarify relationships between orexin A and the hypothalamo-pituitary hormones involved in reproduction. ..
  49. Talmont F, Garcia L, Mazarguil H, Zajac J, Mollereau C. Characterization of two novel tritiated radioligands for labelling Neuropeptide FF (NPFF(1) and NPFF(2)) receptors. Neurochem Int. 2009;55:815-9 pubmed publisher
    ..Therefore, [(3)H]-NPVF and [(3)H]-EYF are new valuable tools for performing binding on NPFF receptors. ..
  50. Yamanaka N, Yamamoto S, Zitnan D, Watanabe K, Kawada T, Satake H, et al. Neuropeptide receptor transcriptome reveals unidentified neuroendocrine pathways. PLoS ONE. 2008;3:e3048 pubmed publisher
    ..This work illustrates how using a combinatorial approach employing bioinformatic, molecular, biochemical and physiological methods can help solve recalcitrant problems in neuropeptide research. ..
  51. Romero C, Ng Y, Luque R, Kineman R, Koch L, Bruning J, et al. Targeted deletion of somatotroph insulin-like growth factor-I signaling in a cell-specific knockout mouse model. Mol Endocrinol. 2010;24:1077-89 pubmed publisher
    ..The SIGFRKO mouse is a model delineating the mechanisms of IGF-I regulation in the hypothalamic-pituitary axis and demonstrates compensatory mechanisms that mediate growth and metabolic function in mammals. ..
  52. Rubio A, Avila J, de Lecea L. Cortistatin as a therapeutic target in inflammation. Expert Opin Ther Targets. 2007;11:1-9 pubmed
    ..In this review, the authors address a new possible role for CST in the immune system and evaluate the possible therapeutic use of CST to treat disorders associated with inflammation. ..
  53. Tang J, Chen J, Ramanjaneya M, Punn A, Conner A, Randeva H. The signalling profile of recombinant human orexin-2 receptor. Cell Signal. 2008;20:1651-61 pubmed publisher