open access

Vol 15, No 3 (2018)
Review paper
Published online: 2018-09-24
Get Citation

An „old” and „new” neuropeptides as modulators of the stress axis (hypothalamus–pituitary–adrenal)

Miłosz Jan Gołyszny
Psychiatria 2018;15(3):135-147.

open access

Vol 15, No 3 (2018)
Prace poglądowe - nadesłane
Published online: 2018-09-24

Abstract

Chronic stress or frequent episodes of exposure to stressors lead to overactivity of neurohormonal systems. A high level
of stress results in an attempt to homeostasis normalization via adaptive changes in neurohormonal systems, neurotransmission
and neuromodulation.
The main neurohormonal stress system is the HPA axis. This axis function is modulated by the action of the neurotransmitters
and also peptide neuromodulators (neuropeptides) — well-known, such as arginine-vasopressin peptide
(AVP), oxytocin (OXT) and relatively recently known, such as orexins (OXs), nesfatin-1, phoenixin (PNX), spexin (SPX),
neuropeptide S (NPS), relaxin-3 (RLN-3). The role of neuropeptides in this modulation is important and may become
a therapeutic target in the future, in neuropsychopharmacology point of view.
The analysis of the works published in recent years clearly confirms, that substances, currently known as neuropeptides
are involved in regulation of the stress axis (HPA). Neuropeptides are involved not only in simply modulation of the
neurohormonal axis, but also many of them characterized anxiogenic or anxiolytic potential.
Currently, new therapeutic targets are researching in affective disturbances neuropsychopharmacology. An increasing
knowledge about neuropeptides should focus the new researches on the modulation of neuropeptide transmission in
order to modernize and improve the therapy of affective disorders.
In the future, neuropeptides may become the main target for the thymoleptic and anxiolytic drugs, however knowledge
about regulation of the HPA axis must be permanent increase about mechanisms of the neuropeptide modulation (well-
-known neuropeptides) and also about new peptides in the OUN (such as cited in the article).

Abstract

Chronic stress or frequent episodes of exposure to stressors lead to overactivity of neurohormonal systems. A high level
of stress results in an attempt to homeostasis normalization via adaptive changes in neurohormonal systems, neurotransmission
and neuromodulation.
The main neurohormonal stress system is the HPA axis. This axis function is modulated by the action of the neurotransmitters
and also peptide neuromodulators (neuropeptides) — well-known, such as arginine-vasopressin peptide
(AVP), oxytocin (OXT) and relatively recently known, such as orexins (OXs), nesfatin-1, phoenixin (PNX), spexin (SPX),
neuropeptide S (NPS), relaxin-3 (RLN-3). The role of neuropeptides in this modulation is important and may become
a therapeutic target in the future, in neuropsychopharmacology point of view.
The analysis of the works published in recent years clearly confirms, that substances, currently known as neuropeptides
are involved in regulation of the stress axis (HPA). Neuropeptides are involved not only in simply modulation of the
neurohormonal axis, but also many of them characterized anxiogenic or anxiolytic potential.
Currently, new therapeutic targets are researching in affective disturbances neuropsychopharmacology. An increasing
knowledge about neuropeptides should focus the new researches on the modulation of neuropeptide transmission in
order to modernize and improve the therapy of affective disorders.
In the future, neuropeptides may become the main target for the thymoleptic and anxiolytic drugs, however knowledge
about regulation of the HPA axis must be permanent increase about mechanisms of the neuropeptide modulation (well-
-known neuropeptides) and also about new peptides in the OUN (such as cited in the article).

Get Citation

Keywords

neuropeptides, stress, HPA

About this article
Title

An „old” and „new” neuropeptides as modulators of the stress axis (hypothalamus–pituitary–adrenal)

Journal

Psychiatria (Psychiatry)

Issue

Vol 15, No 3 (2018)

Article type

Review paper

Pages

135-147

Published online

2018-09-24

Bibliographic record

Psychiatria 2018;15(3):135-147.

Keywords

neuropeptides
stress
HPA

Authors

Miłosz Jan Gołyszny

References (125)
  1. Kozłowski S, Nazar K. Stres. In: Wprowadzenie do fizjologii klinicznej. Wydawnictwo Lekarskie PZWL, Warszawa : 611–630.
  2. Longstaff A. Neurobiologia. Wydawnictwo Naukowe PWN, Warszawa 2002.
  3. Sapolsky RM. Pokonać stres. Świat Nauki. 2003(10): 69–77.
  4. Seta KA, Jansen HT, Kreitel KD, et al. Cold water swim stress increases the expression of neurotensin mRNA in the lateral hypothalamus and medial preoptic regions of the rat brain. Brain Res Mol Brain Res. 2001; 86(1-2): 145–152.
  5. Tamashiro KLK, Nguyen MMN, Sakai RR. Social stress: from rodents to primates. Front Neuroendocrinol. 2005; 26(1): 27–40.
  6. Selye H. Stress, cancer, and the mind. In: Selye H. ed. Cancer, stress, and death. Springer, Boston 1978: 11–19.
  7. Landowski J. Neurobiology of stress. Neuropsychiatria i Neuropsychologia/Neuropsychiatry and Neuropsychology. 2007; 2(1): 26–36.
  8. Hatzinger M. Neuropeptides and the Hypothalamic-Pituitary-Adrenocortical (HPA) System: Review of Recent Research Strategies in Depression. The World Journal of Biological Psychiatry. 2009; 1(2): 105–111.
  9. Herman JP, Ostrander MM, Mueller NK, et al. Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(8): 1201–1213.
  10. Madarasz TJ, Diaz-Mataix L, Akhand O, et al. Brain mechanisms of emotion and emotional learning. Curr Opin Neurobiol. 1992; 2(2): 191–197.
  11. Hamann SB, Ely TD, Grafton ST, et al. Amygdala activity related to enhanced memory for pleasant and aversive stimuli. Nat Neurosci. 1999; 2(3): 289–293.
  12. Phelps EA. Human emotion and memory: interactions of the amygdala and hippocampal complex. Curr Opin Neurobiol. 2004; 14(2): 198–202.
  13. Tafet GE, Bernardini R. Psychoneuroendocrinological links between chronic stress and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27(6): 893–903.
  14. Zagrodzka J. Neurofizjologiczne mechanizmy zachowania emocjonalnego. In: Górska T, Grabowska A, Zagrodzka J. ed. Mózg a zachowanie. Wydanie III. Wydawnictwo Naukowe PWN, Warszawa 2012: 396–415.
  15. Deakin JFW. Distinct roles of 5HT subsystems in panic, anxiety and depression. In: Racagni G, Brunello N, Fokuda T. ed. Biological psychiatry. Elsevier, Amsterdam 1991: 305–307.
  16. Kennett G, Dickinson S, Curzon G. Enhancement of some 5-HT-dependent behavioural responses following repeated immobilization in rats. Brain Research. 1985; 330(2): 253–263.
  17. Tzschentke TM. Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Prog Neurobiol. 2001; 63(3): 241–320.
  18. Cabib S, Puglisi-Allegra S. Different effects of repeated stressful experiences on mesocortical and mesolimbic dopamine metabolism. Neuroscience. 1996; 73(2): 375–380.
  19. Charney D. Psychobiological Mechanisms of Resilience and Vulnerability. FOCUS. 2004; 2(3): 368–391.
  20. Morilak DA, Barrera G, Echevarria DJ, et al. Role of brain norepinephrine in the behavioral response to stress. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(8): 1214–1224.
  21. Herman JP, Tasker JG, Ziegler DR, et al. Local circuit regulation of paraventricular nucleus stress integration: glutamate-GABA connections. Pharmacol Biochem Behav. 2002; 71(3): 457–468.
  22. Nair SM, Werkman TR, Craig J, et al. Corticosteroid regulation of ion channel conductances and mRNA levels in individual hippocampal CA1 neurons. J Neurosci. 1998; 18(7): 2685–2696.
  23. Cullinan WE, Wolfe TJ. Chronic stress regulates levels of mRNA transcripts encoding beta subunits of the GABA(A) receptor in the rat stress axis. Brain Res. 2000; 887(1): 118–124.
  24. Gunnar M, Quevedo K. The neurobiology of stress and development. Annu Rev Psychol. 2007; 58: 145–173.
  25. Palkovits M. Organization of the stress response at the anatomical level. Prog Brain Res. 1987; 72: 47–55.
  26. Bracha HS, Ralston TC, Matsukawa JM, et al. Does "fight or flight" need updating? Psychosomatics. 2004; 45(5): 448–449.
  27. Stuchlíková E, Hrusková J, Hrůza Z, et al. [Lipid metabolism and aging. I. Effect of adrenaline on lipolysis and glycogenolysis in relation to age and stress]. Sb Lek. 1966; 68(7): 207–215.
  28. Haddy R, Clover R. The biological processes in psychological stress. Families, Systems, & Health. 2001; 19(3): 291–302.
  29. Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000; 57(10): 925–935.
  30. Valentino RJ, Foote SL, Page ME. The locus coeruleus as a site for integrating corticotropin-releasing factor and noradrenergic mediation of stress responses. Ann N Y Acad Sci. 1993; 697: 173–188.
  31. Gunnar MR, Vazquez DM, Cicchetti D, et al. Developmental psychopathology. Developmental Neuroscience. 2006.
  32. Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009; 10(6): 397–409.
  33. De Kl. Brain corticosteroid receptor balance and homeostatic control. Front Neuroendocrinol. 1991; 12: 95–164.
  34. De Kloet ER, Vreugdenhil E, Oitzl MS, et al. Brain corticosteroid receptor balance in health and disease. Endocr Rev. 1998; 19(3): 269–301.
  35. Jensen P, Toates FM. Stress as a state of motivational systems. Applied Animal Behaviour Science. 1997; 53(1-2): 145–156.
  36. Ehlert U, Gaab J, Heinrichs M. Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis. Biol Psychol. 2001; 57(1-3): 141–152.
  37. Porter RJ, Gallagher P. Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments. Acta Neuropsychiatr. 2006; 18(5): 193–209.
  38. Tarcic N, Ovadia H, Weiss DW, et al. Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids. J Neuroimmunol. 1998; 82(1): 40–46.
  39. Tuli JS, Smith JA, Morton DB. Corticosterone, adrenal and spleen weight in mice after tail bleeding, and its effect on nearby animals. Lab Anim. 1995; 29(1): 90–95.
  40. De Wied D, Jolles J. Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects. Physiol Rev. 1982; 62(3): 976–1059.
  41. Reiner A. A comparison of neurotransmitter-specific and neuropeptide-specific neuronal cell types present in the dorsal cortex in turtles with those present in the isocortex in mammals: implications for the evolution of isocortex. Brain Behav Evol. 1991; 38(2-3): 53–91.
  42. Ludwig M, Leng G. Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci. 2006; 7(2): 126–136.
  43. Aguilera G. Regulation of pituitary ACTH secretion during chronic stress. Frontiers in neuroendocrinology. 1994; 15(4): 321–350.
  44. Murgatroyd C, Spengler D. Epigenetic programming of the HPA axis: early life decides. Stress. 2011; 14(6): 581–589.
  45. Frank E, Landgraf R. The vasopressin system--from antidiuresis to psychopathology. Eur J Pharmacol. 2008; 583(2-3): 226–242.
  46. Wigger A, Sánchez MM, Mathys KC, et al. Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: critical role of vasopressin. Neuropsychopharmacology. 2004; 29(1): 1–14.
  47. Griebel G, Simiand J, Serradeil-Le Gal C, et al. Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci U S A. 2002; 99(9): 6370–6375.
  48. Zelena D, Jain SK. Another side of the antidiuretic hormone, vasopressin: its role in stress regulation. Journal of Experimental Sciences. 2011; 1(9).
  49. Landgraf R, Gerstberger R, Montkowski A, et al. V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci. 1995; 15(6): 4250–4258.
  50. Rinaman L, Sherman TG, Stricker EM. Vasopressin and oxytocin in the central nervous system. In: Kupfer F, Sherman TG, Stricker EM. ed. Psychopharmacology: the fourth generation of progress. Raven, New York 1995: 531–542.
  51. Churchland PS, Winkielman P. Modulating social behavior with oxytocin: how does it work? What does it mean? Horm Behav. 2012; 61(3): 392–399.
  52. Soloff MS. Regulation of oxytocin action at the receptor level. Life Sci. 1979; 25(17): 1453–1460.
  53. Windle RJ, Kershaw YM, Shanks N, et al. Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity. J Neurosci. 2004; 24(12): 2974–2982.
  54. Zheng J, Babygirija R, Bülbül M, et al. Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats. Am J Physiol Gastrointest Liver Physiol. 2010; 299(4): G946–G953.
  55. Windle RJ, Shanks N, Lightman SL, et al. Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology. 1997; 138(7): 2829–2834.
  56. Parker KJ, Buckmaster CL, Schatzberg AF, et al. Intranasal oxytocin administration attenuates the ACTH stress response in monkeys. Psychoneuroendocrinology. 2005; 30(9): 924–929.
  57. Uvnäs-Moberg K, Ahlenius S, Hillegaart V, et al. High doses of oxytocin cause sedation and low doses cause an anxiolytic-like effect in male rats. Pharmacol Biochem Behav. 1994; 49(1): 101–106.
  58. Larhammar D. Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide. Regulatory Peptides. 1996; 62(1): 1–11.
  59. Liposits Z, Sievers L, Paull WK. Neuropeptide-Y and ACTH-immunoreactive innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamus of the rat. An immunocytochemical analysis at the light and electron microscopic levels. Histochemistry. 1988; 88(3-6): 227–234.
  60. Sawchenko PE, Swanson LW, Grzanna R, et al. Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol. 1985; 241(2): 138–153.
  61. Blomqvist AG, Herzog H. Y-receptor subtypes--how many more? Trends Neurosci. 1997; 20(7): 294–298.
  62. Suda T, Tozawa F, Iwai I, et al. Neuropeptide Y increases the corticotropin-releasing factor messenger ribonucleic acid level in the rat hypothalamus. Brain Res Mol Brain Res. 1993; 18(4): 311–315.
  63. Husum H, Termeer E, Mathé AA, et al. Early maternal deprivation alters hippocampal levels of neuropeptide Y and calcitonin-gene related peptide in adult rats. Neuropharmacology. 2002; 42(6): 798–806.
  64. Widerlov E, Wahlestedt C, Hakanson R, et al. Altered brain neuropeptide function in psychiatric illnesses-with special emphasis on NPY and CRF in major depression. Clinical Neuropharmacology. 1986; 9: 572–574.
  65. Westrin A. Stress system alterations and mood disorders in suicidal patients. A review. Biomed Pharmacother. 2000; 54(3): 142–145.
  66. Redrobe JP, Dumont Y, Fournier A, et al. The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neuropsychopharmacology. 2002; 26(5): 615–624.
  67. Ishida H, Shirayama Y, Iwata M, et al. Infusion of neuropeptide Y into CA3 region of hippocampus produces antidepressant-like effect via Y1 receptor. Hippocampus. 2007; 17(4): 271–280.
  68. Kokare DM, Dandekar MP, Chopde CT, et al. Interaction between neuropeptide Y and alpha-melanocyte stimulating hormone in amygdala regulates anxiety in rats. Brain Res. 2005; 1043(1-2): 107–114.
  69. Karlsson RM, Holmes A, Heilig M, et al. Anxiolytic-like actions of centrally-administered neuropeptide Y, but not galanin, in C57BL/6J mice. Pharmacol Biochem Behav. 2005; 80(3): 427–436.
  70. Britton KT, Akwa Y, Spina MG, et al. Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze. Peptides. 2000; 21(1): 37–44.
  71. Kastin AJ, Akerstrom V. Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther. 1999; 289(1): 219–223.
  72. Date Y, Ueta Y, Yamashita H, et al. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci U S A. 1999; 96(2): 748–753.
  73. Ciriello J, Rosas-Arellano MP, Solano-Flores LP, et al. Identification of neurons containing orexin-B (hypocretin-2) immunoreactivity in limbic structures. Brain Res. 2003; 967(1-2): 123–131.
  74. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998; 92(4): 573–585.
  75. Taheri S, Bloom S. Orexins/hypocretins: waking up the scientific world. Clin Endocrinol (Oxf). 2001; 54(4): 421–429.
  76. Zhu Y, Miwa Y, Yamanaka A, et al. 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. 2003; 92(3): 259–266.
  77. Smart D, Jerman JC, Brough SJ, et al. Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR. Br J Pharmacol. 1999; 128(1): 1–3.
  78. Winsky-Sommerer R, Yamanaka A, Diano S, et al. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci. 2004; 24(50): 11439–11448.
  79. Sakamoto F, Yamada S, Ueta Y. Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: possible involvement of central orexins on stress-activated central CRF neurons. Regul Pept. 2004; 118(3): 183–191.
  80. Samson WK, Taylor MM, Follwell M, et al. Orexin actions in hypothalamic paraventricular nucleus: physiological consequences and cellular correlates. Regul Pept. 2002; 104(1-3): 97–103.
  81. Mazzocchi G, Malendowicz LK, Gottardo L, et al. Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade. J Clin Endocrinol Metab. 2001; 86(2): 778–782.
  82. Malendowicz LK, Tortorella C, Nussdorfer GG. Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade. J Steroid Biochem Mol Biol. 1999; 70(4-6): 185–188.
  83. Kuru M, Ueta Y, Serino R, et al. Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport. 2000; 11(9): 1977–1980.
  84. Brundin L, Björkqvist M, Petersén A, et al. Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder. Eur Neuropsychopharmacol. 2007; 17(9): 573–579.
  85. Shimizu H, Ohsaki A, Oh-I S, et al. A new anorexigenic protein, nesfatin-1. Peptides. 2009; 30(5): 995–998.
  86. Gaigé S, Bonnet MS, Tardivel C, et al. c-Fos immunoreactivity in the pig brain following deoxynivalenol intoxication: focus on NUCB2/nesfatin-1 expressing neurons. Neurotoxicology. 2013; 34: 135–149.
  87. Goebel M, Stengel A, Wang L, et al. Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett. 2009; 452(3): 241–246.
  88. Goebel-Stengel M, Wang L, Stengel A, et al. Localization of nesfatin-1 neurons in the mouse brain and functional implication. Brain Res. 2011; 1396: 20–34.
  89. Goebel-Stengel M, Wang L. Central and peripheral expression and distribution of NUCB2/nesfatin-1. Curr Pharm Des. 2013; 19(39): 6935–6940.
  90. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab. 2009; 10(5): 355–365.
  91. Merali Z, Cayer C, Kent P, et al. Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology (Berl). 2008; 201(1): 115–123.
  92. Yoshida N, Maejima Y, Sedbazar U, et al. Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis. Aging (Albany NY). 2010; 2(11): 775–784.
  93. Foo KS, Brismar H, Broberger C. Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. Neuroscience. 2008; 156(3): 563–579.
  94. Price CJ, Hoyda TD, Samson WK, et al. Nesfatin-1 influences the excitability of paraventricular nucleus neurones. J Neuroendocrinol. 2008; 20(2): 245–250.
  95. Könczöl K, Bodnár I, Zelena D, et al. Nesfatin-1/NUCB2 may participate in the activation of the hypothalamic-pituitary-adrenal axis in rats. Neurochem Int. 2010; 57(3): 189–197.
  96. Okere B, Xu Lu, Roubos EW, et al. Restraint stress alters the secretory activity of neurons co-expressing urocortin-1, cocaine- and amphetamine-regulated transcript peptide and nesfatin-1 in the mouse Edinger-Westphal nucleus. Brain Res. 2010; 1317: 92–99.
  97. Yosten GLC, Lyu RM, Hsueh AJW, et al. A novel reproductive peptide, phoenixin. J Neuroendocrinol. 2013; 25(2): 206–215.
  98. Lyu RM, Huang XF, Zhang Y, et al. Phoenixin: a novel peptide in rodent sensory ganglia. Neuroscience. 2013; 250: 622–631.
  99. Hofmann T, Weibert E, Ahnis A, et al. Phoenixin is negatively associated with anxiety in obese men. Peptides. 2017; 88: 32–36.
  100. Gasparini S, Stein LM, Loewen SP, et al. Novel regulator of vasopressin secretion: phoenixin. Am J Physiol Regul Integr Comp Physiol. 2018; 314(4): R623–R628.
  101. Jiang JH, He Z, Peng YL, et al. Effects of Phoenixin-14 on anxiolytic-like behavior in mice. Behav Brain Res. 2015; 286: 39–48.
  102. Porzionato A, Rucinski M, Macchi V, et al. Spexin expression in normal rat tissues. J Histochem Cytochem. 2010; 58(9): 825–837.
  103. Porzionato A, Rucinski M, Macchi V, et al. Spexin is expressed in the carotid body and is upregulated by postnatal hyperoxia exposure. Adv Exp Med Biol. 2012; 758: 207–213.
  104. Kim DK, Yun S, Son GiH, et al. Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III. Endocrinology. 2014; 155(5): 1864–1873.
  105. Wong MKH, Sze KH, Chen T, et al. Goldfish spexin: solution structure and novel function as a satiety factor in feeding control. Am J Physiol Endocrinol Metab. 2013; 305(3): E348–E366.
  106. Li S, Liu Q, Xiao L, et al. Molecular cloning and functional characterization of spexin in orange-spotted grouper (Epinephelus coioides). Comp Biochem Physiol B Biochem Mol Biol. 2016; 196-197: 85–91.
  107. Rucinski M, Porzionato A, Ziolkowska A, et al. Expression of the spexin gene in the rat adrenal gland and evidences suggesting that spexin inhibits adrenocortical cell proliferation. Peptides. 2010; 31(4): 676–682.
  108. Xu YL, Reinscheid RK, Huitron-Resendiz S, et al. Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects. Neuron. 2004; 43(4): 487–497.
  109. Reinscheid RK, Xu YL, Okamura N, et al. Pharmacological characterization of human and murine neuropeptide s receptor variants. J Pharmacol Exp Ther. 2005; 315(3): 1338–1345.
  110. Xu YL, Gall CM, Jackson VR, et al. Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain. J Comp Neurol. 2007; 500(1): 84–102.
  111. Pape HC, Jüngling K, Seidenbecher T, et al. Neuropeptide S: a transmitter system in the brain regulating fear and anxiety. Neuropharmacology. 2010; 58(1): 29–34.
  112. Gupte J, Cutler G, Chen JL, et al. Elucidation of signaling properties of vasopressin receptor-related receptor 1 by using the chimeric receptor approach. Proc Natl Acad Sci U S A. 2004; 101(6): 1508–1513.
  113. Pañeda C, Huitron-Resendiz S, Frago LM, et al. Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice. J Neurosci. 2009; 29(13): 4155–4161.
  114. Ionescu IA, Dine J, Yen YC, et al. Intranasally administered neuropeptide S (NPS) exerts anxiolytic effects following internalization into NPS receptor-expressing neurons. Neuropsychopharmacology. 2012; 37(6): 1323–1337.
  115. Shan J, Krukoff TL. Distribution of preproadrenomedullin mRNA in the rat central nervous system and its modulation by physiological stressors. J Comp Neurol. 2001; 432(1): 88–100.
  116. Holets VR, Hökfelt T, Rökaeus A, et al. Locus coeruleus neurons in the rat containing neuropeptide Y, tyrosine hydroxylase or galanin and their efferent projections to the spinal cord, cerebral cortex and hypothalamus. Neuroscience. 1988; 24(3): 893–906.
  117. Bathgate RAD, Samuel CS, Burazin TCD, et al. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. J Biol Chem. 2002; 277(2): 1148–1157.
  118. Liu C, Eriste E, Sutton S, et al. Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135. J Biol Chem. 2003; 278(50): 50754–50764.
  119. Tanaka M, Iijima N, Miyamoto Y, et al. Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress. Eur J Neurosci. 2005; 21(6): 1659–1670.
  120. Banerjee A, Shen PJ, Ma S, et al. Swim stress excitation of nucleus incertus and rapid induction of relaxin-3 expression via CRF1 activation. Neuropharmacology. 2010; 58(1): 145–155.
  121. Ryan PJ, Ma S, Olucha-Bordonau FE, et al. Nucleus incertus--an emerging modulatory role in arousal, stress and memory. Neurosci Biobehav Rev. 2011; 35(6): 1326–1341.
  122. Watanabe Y, Miyamoto Y, Matsuda T, et al. Relaxin-3/INSL7 regulates the stress-response system in the rat hypothalamus. J Mol Neurosci. 2011; 43(2): 169–174.
  123. Watanabe Y, Tsujimura A, Takao K, et al. Relaxin-3-deficient mice showed slight alteration in anxiety-related behavior. Front Behav Neurosci. 2011; 5: 50.
  124. Ryan PJ, Büchler E, Shabanpoor F, et al. Central relaxin-3 receptor (RXFP3) activation decreases anxiety- and depressive-like behaviours in the rat. Behav Brain Res. 2013; 244: 142–151.
  125. McGowan BM, Stanley SA, Donovan J, et al. Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis. Am J Physiol Endocrinol Metab. 2008; 295(2): E278–E286.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest Via Medica sp. z o.o. sp. komandytowa, ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl