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Intracellular Signal Pathways Utilized by the Hypocretin/Orexin Receptors

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Hypocretins

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6. References

  1. J. Näsman, J. P. Kukkonen, T. Holmqvist and K. E. Åkerman, Different roles for Gi and Go proteins in modulation of adenylyl cyclase type-2 activity, J Neurochem. 83, 1252–61 (2002).

    Article  PubMed  Google Scholar 

  2. A. E. Brady and L. E. Limbird, G protein-coupled receptor interacting proteins: emerging roles in localization and signal transduction, Cell Signal. 14, 297–309 (2002).

    Article  PubMed  CAS  Google Scholar 

  3. C. Heuss and U. Gerber, G-protein-independent signaling by G-protein-coupled receptors, Trends Neurosci. 23, 469–75 (2000).

    Article  PubMed  CAS  Google Scholar 

  4. E. Karteris, H. S. Randeva, D. K. Grammatopoulos, R. B. Jaffe and E. W. Hillhouse, Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals, J Clin Endocrinol Metab. 86, 4512–9 (2001).

    Article  PubMed  CAS  Google Scholar 

  5. H. S. Randeva, E. Karteris, D. Grammatopoulos and E. W. Hillhouse, Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis, J Clin Endocrinol Metab. 86, 4808–13 (2001).

    Article  PubMed  CAS  Google Scholar 

  6. R. Bernard, R. Lydic and H. A. Baghdoyan, Hypocretin-1 activates G proteins in arousal-related brainstem nuclei of rat, Neuroreport. 13, 447–50 (2002).

    Article  PubMed  CAS  Google Scholar 

  7. R. Bernard, R. Lydic and H. A. Baghdoyan, Hypocretin-1 causes G protein activation and increases ACh release in rat pons, Eur J Neurosci. 18, 1775–85 (2003).

    Article  PubMed  Google Scholar 

  8. L. de Lecea, T. S. Kilduff, C. Peyron, X. Gao, P. E. Foye, P. E. Danielson, C. Fukuhara, E. L. Battenberg, V. T. Gautvik, F. S. Bartlett, 2nd, W. N. Frankel, A. N. van den Pol, F. E. Bloom, K. M. Gautvik and J. G. Sutcliffe, The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity, Proc Natl Acad Sci U S A. 95, 322–7 (1998).

    Article  PubMed  Google Scholar 

  9. B. M. Ances, J. H. Greenberg and J. A. Detre, Effects of variations in interstimulus interval on activation-flow coupling response and somatosensory evoked potentials with forepaw stimulation in the rat, J Cereb Blood Flow Metab. 20, 290–7 (2000).

    Article  PubMed  CAS  Google Scholar 

  10. Q. V. Hoang, D. Bajic, M. Yanagisawa, S. Nakajima and Y. Nakajima, Effects of orexin (hypocretin) on GIRK channels, J Neurophysiol. 90, 693–702 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. B. Yang and A. V. Ferguson, Orexin-A depolarizes nucleus tractus solitarius neurons through effects on nonselective cationic and K+ conductances, J Neurophysiol. 89, 2167–75 (2003).

    Article  PubMed  CAS  Google Scholar 

  12. K. Uramura, H. Funahashi, S. Muroya, S. Shioda, M. Takigawa and T. Yada, Orexin-a activates phospholipase C-and protein kinase C-mediated Ca2+ signaling in dopamine neurons of the ventral tegmental area, Neuroreport. 12, 1885–9. (2001).

    Article  PubMed  CAS  Google Scholar 

  13. A. N. Van Den Pol, P. R. Patrylo, P. K. Ghosh and X. B. Gao, Lateral hypothalamus: Early developmental expression and response to hypocretin (orexin), J Comp Neurol. 433, 349–363. (2001).

    Article  Google Scholar 

  14. K. A. Kohlmeier, T. Inoue and C. S. Leonard, Hypocretin/orexin peptide signaling in the ascending arousal system: elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum, J Neurophysiol. 92, 221–35 (2004).

    Article  PubMed  CAS  Google Scholar 

  15. T. M. Korotkova, K. S. Eriksson, H. L. Haas and R. E. Brown, Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/hypocretin in vitro, Regul Pept. 104, 83–89 (2002).

    Article  PubMed  CAS  Google Scholar 

  16. R. E. Brown, O. Sergeeva, K. S. Eriksson and H. L. Haas, Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat, Neuropharmacology. 40, 457–9. (2001).

    Article  PubMed  CAS  Google Scholar 

  17. K. Hirota, T. Kushikata, M. Kudo, T. Kudo, D. G. Lambert and A. Matsuki, Orexin A and B evoke noradrenaline release from rat cerebrocortical slices, Br J Pharmacol. 134, 1461–6 (2001).

    Article  PubMed  CAS  Google Scholar 

  18. M. Rauch, T. Riediger, H. A. Schmid and E. Simon, Orexin A activates leptin-responsive neurons in the arcuate nucleus, Pflugers Arch. 440, 699–703. (2000).

    Article  PubMed  CAS  Google Scholar 

  19. D. Burdakov, B. Liss and F. M. Ashcroft, Orexin excites GABAergic neurons of the arcuate nucleus by activating the sodium—calcium exchanger, J Neurosci. 23, 4951–7 (2003).

    PubMed  CAS  Google Scholar 

  20. J. J. Hwang, V. J. Dzau and C. C. Liew, Genomics and the pathophysiology of heart failure, Curr Cardiol Rep. 3, 198–207 (2001).

    PubMed  CAS  Google Scholar 

  21. G. Grabauskas and H. C. Moises, Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin, J Physiol. 549, 37–56 (2003).

    Article  PubMed  CAS  Google Scholar 

  22. S. Burlet, C. J. Tyler and C. S. Leonard, Direct and indirect excitation of laterodorsal tegmental neurons by Hypocretin/Orexin peptides: implications for wakefulness and narcolepsy, J Neurosci. 22, 2862–72 (2002).

    PubMed  CAS  Google Scholar 

  23. K. A. Kohlmeier, T. Inoue and C. S. Leonard, Hypocretin/Orexin peptide signalling in the ascending arousal system: Elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum, J Neurophysiol. (2004).

    Google Scholar 

  24. R. E. Brown, O. A. Sergeeva, K. S. Eriksson and H. L. Haas, Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline), J Neurosci. 22, 8850–9 (2002).

    PubMed  CAS  Google Scholar 

  25. R. J. Liu, A. N. van den Pol and G. K. Aghajanian, Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions, J Neurosci. 22, 9453–64 (2002).

    PubMed  CAS  Google Scholar 

  26. T. L. Horvath, C. Peyron, S. Diano, A. Ivanov, G. Aston-Jones, T. S. Kilduff and A. N. van Den Pol, Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system, J Comp Neurol. 415, 145–59 (1999).

    Article  PubMed  CAS  Google Scholar 

  27. A. Ivanov and G. Aston-Jones, Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons, Neuroreport. 11, 1755–8. (2000).

    Article  PubMed  CAS  Google Scholar 

  28. A. N. van den Pol, X. B. Gao, K. Obrietan, T. S. Kilduff and A. B. Belousov, Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin, J Neurosci. 18, 7962–71 (1998).

    PubMed  Google Scholar 

  29. L. I. Kiyashchenko, B. Y. Mileykovskiy, N. Maidment, H. A. Lam, M. F. Wu, J. John, J. Peever and J. M. Siegel, Release of hypocretin (orexin) during waking and sleep states, J Neurosci. 22, 5282–6 (2002).

    PubMed  CAS  Google Scholar 

  30. M. Wu, L. Zaborszky, T. Hajszan, A. N. van den Pol and M. Alreja, Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons, J Neurosci. 24, 3527–36 (2004).

    Article  PubMed  CAS  Google Scholar 

  31. L. L. Hwang, C. T. Chen and N. J. Dun, Mechanisms of orexin-induced depolarizations in rat dorsal motor nucleus of vagus neurones in vitro, J Physiol. 537, 511–20 (2001).

    Article  PubMed  CAS  Google Scholar 

  32. D. E. Clapham, TRP channels as cellular sensors, Nature. 426, 517–24 (2003).

    Article  PubMed  CAS  Google Scholar 

  33. O. A. Sergeeva, T. M. Korotkova, A. Scherer, R. E. Brown and H. L. Haas, Co-expression of non-selective cation channels of the transient receptor potential canonical family in central aminergic neurones, J Neurochem. 85, 1547–52 (2003).

    Article  PubMed  CAS  Google Scholar 

  34. K. S. Eriksson, O. Sergeeva, R. E. Brown and H. L. Haas, Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus, J Neurosci. 21, 9273–9 (2001).

    PubMed  CAS  Google Scholar 

  35. B. Linck, Z. Qiu, Z. He, Q. Tong, D. W. Hilgemann and K. D. Philipson, Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3), Am J Physiol. 274, C415–23 (1998).

    PubMed  CAS  Google Scholar 

  36. T. Iwamoto and S. Kita, Development and application of Na+/Ca2+ exchange inhibitors, Mol Cell Biochem. 259, 157–61 (2004).

    Article  PubMed  CAS  Google Scholar 

  37. J. P. Kukkonen, T. Holmqvist, S. Ammoun and K. E. Akerman, Functions of the orexinergic/ hypocretinergic system, Am J Physiol Cell Physiol. 283, C1567–91 (2002).

    PubMed  CAS  Google Scholar 

  38. M. L. Barreiro, R. Pineda, V. M. Navarro, M. Lopez, J. S. Suominen, L. Pinilla, R. Senaris, J. Toppari, E. Aguilar, C. Dieguez and M. Tena-Sempere, Orexin 1 receptor messenger ribonucleic acid expression and stimulation of testosterone secretion by orexin-A in rat testis, Endocrinology. 145, 2297–306 (2004).

    Article  PubMed  CAS  Google Scholar 

  39. E. Karteris, J. Chen and H. S. Randeva, Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system, J Clin Endocrinol Metab. 89, 1957–62 (2004).

    Article  PubMed  CAS  Google Scholar 

  40. L. K. Malendowicz, C. Tortorella and G. G. Nussdorfer, Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade, J Steroid Biochem Mol Biol. 70, 185–8 (1999).

    Article  PubMed  CAS  Google Scholar 

  41. G. Mazzocchi, L. K. Malendowicz, L. Gottardo, F. Aragona and G. G. Nussdorfer, Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade, J Clin Endocrinol Metab. 86, 778–82. (2001).

    Article  PubMed  CAS  Google Scholar 

  42. T. Nanmoku, K. Isobe, T. Sakurai, A. Yamanaka, K. Takekoshi, Y. Kawakami, K. Goto and T. Nakai, Effects of orexin on cultured porcine adrenal medullary and cortex cells, Regul Pept. 104, 125–130 (2002).

    Article  PubMed  CAS  Google Scholar 

  43. R. Xu, Q. Wang, M. Yan, M. Hernandez, C. Gong, W. C. Boon, Y. Murata, Y. Ueta and C. Chen, Orexin-A augments voltage-gated Ca2+ currents and synergistically increases growth hormone (GH) secretion with GH-releasing hormone in primary cultured ovine somatotropes, Endocrinology. 143, 4609–19 (2002).

    Article  PubMed  CAS  Google Scholar 

  44. K. P. Larsson, K. E. Akerman, J. Magga, S. Uotila, J. P. Kukkonen, J. Nasman and K. H. Herzig, The STC-1 cells express functional orexin-A receptors coupled to CCK release, Biochem Biophys Res Commun. 309, 209–16 (2003).

    Article  PubMed  CAS  Google Scholar 

  45. D. Smart, J. C. Jerman, S. J. Brough, W. A. Neville, F. Jewitt and R. A. Porter, The hypocretins are weak agonists at recombinant human orexin-1 and orexin-2 receptors, Br J Pharmacol. 129, 1289–91 (2000).

    Article  PubMed  CAS  Google Scholar 

  46. T. Sakurai, A. Amemiya, M. Ishii, I. Matsuzaki, R. M. Chemelli, H. Tanaka, S. C. Williams, J. A. Richardson, G. P. Kozlowski, S. Wilson, J. R. Arch, R. E. Buckingham, A. C. Haynes, S. A. Carr, R. S. Annan, D. E. McNulty, W. S. Liu, J. A. Terrett, N. A. Elshourbagy, D. J. Bergsma and M. Yanagisawa, Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior, Cell. 92, 573–85 (1998).

    Article  PubMed  CAS  Google Scholar 

  47. P. E. Lund, R. Shariatmadari, A. Uustare, M. Detheux, M. Parmentier, J. P. Kukkonen and K. E. Akerman, The Orexin OX1 Receptor Activates a Novel Ca2+ Influx Pathway Necessary for Coupling to Phospholipase C, J Biol Chem. 275, 30806–30812 (2000).

    Article  PubMed  CAS  Google Scholar 

  48. T. Holmqvist, K. E. Akerman and J. P. Kukkonen, Orexin signaling in recombinant neuron-like cells, FEBS Lett. 526, 11–4 (2002).

    Article  PubMed  CAS  Google Scholar 

  49. Y. Zhu, Y. Miwa, A. Yamanaka, T. Yada, M. Shibahara, Y. Abe, T. Sakurai and K. Goto, Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and-insensitive G-proteins, J Pharmacol Sci. 92, 259–66 (2003).

    Article  PubMed  CAS  Google Scholar 

  50. J. P. Kukkonen and K. E. Akerman, Orexin receptors couple to Ca2+ channels different from store-operated Ca2+ channels, Neuroreport. 12, 2017–20 (2001).

    Article  PubMed  CAS  Google Scholar 

  51. S. Ammoun, T. Holmqvist, R. Shariatmadari, H. B. Oonk, M. Detheux, M. Parmentier, K. E. Akerman and J. P. Kukkonen, Distinct recognition of OX1 and OX2 receptors by orexin peptides, J Pharmacol Exp Ther. 305, 507–14 (2003).

    Article  PubMed  CAS  Google Scholar 

  52. Q. V. Hoang, P. Zhao, S. Nakajima and Y. Nakajima, Orexin (Hypocretin) Effects on Constitutively Active Inward Rectifier K+ Channels in Cultured Nucleus Basalis Neurons, J Neurophysiol. (2004).

    Google Scholar 

  53. S. Muroya, H. Funahashi, A. Yamanaka, D. Kohno, K. Uramura, T. Nambu, M. Shibahara, M. Kuramochi, M. Takigawa, M. Yanagisawa, T. Sakurai, S. Shioda and T. Yada, Orexins (hypocretins) directly interact with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca 2+ signaling in a reciprocal manner to leptin: orexigenic neuronal pathways in the mediobasal hypothalamus, Eur J Neurosci. 19, 1524–34 (2004).

    Article  PubMed  Google Scholar 

  54. J. S. Gutkind, Regulation of mitogen-activated protein kinase signaling networks by G protein-coupled receptors, Sci STKE. 2000, RE1 (2000).

    Google Scholar 

  55. T. Gudermann, R. Grosse and G. Schultz, Contribution of receptor/G protein signaling to cell growth and transformation, Naunyn Schmiedebergs Arch Pharmacol. 361, 345–62 (2000).

    Article  PubMed  CAS  Google Scholar 

  56. S. Hilairet, M. Bouaboula, D. Carriere, G. Le Fur and P. Casellas, Hypersensitization of the Orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716, J Biol Chem. 278, 23731–7 (2003).

    Article  PubMed  CAS  Google Scholar 

  57. O. Selbach, N. Doreulee, C. Bohla, K. S. Eriksson, O. A. Sergeeva, W. Poelchen, R. E. Brown and H. L. Haas, Orexins/hypocretins cause sharp wave-and theta-related synaptic plasticity in the hippocampus via glutamatergic, gabaergic, noradrenergic, and cholinergic signaling, Neuroscience. 127, 519–28 (2004).

    Article  PubMed  CAS  Google Scholar 

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  1. Uppsala University, Uppsala, Sweden

    Jyrki P. Kukkonen & Karl E. O. Åkerman

  2. University of Kuopio, Kuopio, Finland

    Karl E. O. Åkerman

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    Luis de Lecea  & J. Gregor Sutcliffe  & 

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Kukkonen, J.P., Åkerman, K.E.O. (2005). Intracellular Signal Pathways Utilized by the Hypocretin/Orexin Receptors. In: de Lecea, L., Sutcliffe, J.G. (eds) Hypocretins. Springer, Boston, MA. https://doi.org/10.1007/0-387-25446-3_14

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