Involvement of neuropeptide Y in neuroendocrine stress responses. Central and peripheral studies

  • P. Mormède
  • V. Castagné
  • J.-M. Rivet
  • R. Gaillard
  • R. Corder
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 29)


Neuropeptide Y (NPY) is closely associated to stress-reactive structures in the central and peripheral nervous system. In the periphery, the peptide is colocalized with catecholamines in postganglionic sympathetic fibres and the adrenal medulla. In the brain, the paraventricular nucleus of the hypothalamus receives a dense innervation of NPYergic neurons, some of which also contain monoamines. With the use of a specific immunoradiometric assay, we have demonstrated that NPY is released into the peripheral circulation during psychological stress together with catecholamines. The postganglionic origin of the peptide was demonstrated by the activity of the nicotinic antagonist hexame-thonium to attenuate the response. Adrenalectomy or insulin-induced hypo-glycemia did not alter basal or stimulated NPY plasma levels, showing that the adrenal is not a major souce of circulating NPY in the rat. Although NPY and noradrenaline are frequently released in parallel in various experimental conditions, a clear dissociation can be found in several cases, such as cold stress or the response to phentolamine, where no change can be seen in plasma NPY despite a large activation of noradrenergic terminals. Furthermore, the neuropeptide may play a role in stress-induced pathological states such as hypertension, since its release is greater in animals previously submitted to chronic stress and high-sodium diet. On the other hand, its role in the central nervous system control mechanisms of the stress response is far from being clear, but to understand the interaction of NPY we need a better knowledge of the role of noradrenergic neurons in the central control of the adrenocortical axis or sympathetic nervous system activity.


Chronic Stress Paraventricular Nucleus Pancreatic Polypeptide Arcuate Nucleus Adrenal Medullary Cell 
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  1. Allen JM, Adrian TE, Polak JM, Bloom SR (1983) Neuropeptide Y (NPY) in the adrenal gland. J Auton Nerv Syst 9: 559–563.PubMedCrossRefGoogle Scholar
  2. Allen JM, Bircham PMM, Bloom SR, Edwards AV (1984) Release of neuropeptide Y in response to splanchnic nerve stimulation in the conscious calf. J Physiol 357: 401–408.PubMedGoogle Scholar
  3. Bai FL, Yamano M, Shiotani Y, Emson PC, Smith AD, Pwell JF, Tohyama M (1985) An arcuato-paraventricular and-dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat. Brain Res 331: 172–175.PubMedCrossRefGoogle Scholar
  4. Castagné V, Corder R, Gaillard R, Mormède P (1987) Stress-induced changes of circulating neuropeptide Y in the rat: comparison with catecholamines. Regul Pept 19: 55–63.PubMedCrossRefGoogle Scholar
  5. Corder R, Lowry PJ (1985) An immunoradiometric assay for the measurement of neuropeptide Y in plasma. Peptides 6: 1195–1200.PubMedCrossRefGoogle Scholar
  6. Corder R, Pralong F, Turnill D, Saudan P, Muller AF, Gaillard RC (1988) Dexamethasone treatment increases neuropeptide Y levels in rat hypothalamic neurones. Life Sci 43: 1879–1886.PubMedCrossRefGoogle Scholar
  7. Corder R, Waeber B, Evequoz D, Nussberger J, Gaillard R, Brunner H (1988) Effect of ganglion blockade with pentolinium on circulating neuropeptide Y levels in conscious rats. J Cardiovasc Pharmacol 12: 140–143.PubMedCrossRefGoogle Scholar
  8. Everitt BJ, Hökfelt T, Terenius L, Tatemoto K, Mutt V, Goldstein M (1984) Differential coexistence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the rat. Neuroscience 11: 443–462.PubMedCrossRefGoogle Scholar
  9. Folkow B (1982) Physiological aspects of primary hypertension. Physiol Rev 62: 347–504.PubMedGoogle Scholar
  10. Ganong WF (1980) Neurotransmitters and pituitary function: regulation of ACTH secretion. Fed Proc 39: 2923–2930.PubMedGoogle Scholar
  11. Gustafson EL, Moore RY (1987) Noradrenaline and neuropeptide Y innervation of the rat hypothalamus are differentially affected by 6-hydroxydopamine. Neurosci Lett 83: 53–58.PubMedCrossRefGoogle Scholar
  12. Gustafsson JA, Carlstedt-Duke J, Poellinger L, Okret S, Wikdtröm AC, Bronnegard M, Gillner M, Dong Y, Fuxe K, Cintra A, Härfstrand A, Agnati L (1987) Biochemistry, molecular biology, and physiology of the glucocorticoid receptor. Endocr Rev 8: 185–234.PubMedCrossRefGoogle Scholar
  13. Härfstrand A, Eneroth P, Agnati L, Fuxe K (1987 a) Further studies on the effects of central administration of neuropeptide Y on neuroendocrine function in the male rat: relationship to hypothalamic catecholamines. Regul Pept 17: 167–179.PubMedCrossRefGoogle Scholar
  14. Härfstrand A, Fuxe K, Terenius L, Kalia M (1987b) Neuropeptide Y-immunoreactive parikarya and nerve terminals in the rat medulla oblongata: relationship to cytoar-chitecture and catecholaminergic cell groups. J Comp Neurol 260: 20–35.PubMedCrossRefGoogle Scholar
  15. Kondo H (1985) Immunohistochemical analysis of the localisation of neuropeptides in the adrenal gland. Arch Histol Jpn 48: 453–481.PubMedCrossRefGoogle Scholar
  16. Kvetnansky R, Sun CL, Lake CR, Thoa N, Torda T, Kopin IJ (1978) Effect of handling and forced immobilization on rat plasma levels of epinephrine, norepinephrine, and dopamine-β-hydroxylase. Endocrinology 103: 1868–1874.PubMedCrossRefGoogle Scholar
  17. Lundberg JM, Tatemoto K (1982) Pancreatic polypeptide family (APP, BPP, NPY, and PYY) in relation to sympathetic vasoconstriction resistant to-adrenoceptor blockade. Acta Physiol Scand 116: 393–402.PubMedCrossRefGoogle Scholar
  18. Lundberg JM, Terenius L, Hökfelt T, Goldstein M (1983) High levels of neuropeptide Y in peripheral noradrenergic neurons in various mammals including man. Neurosci Lett 42: 167–172.PubMedCrossRefGoogle Scholar
  19. Lundberg JM, Martinsson A, Hemsén A, Theodorsson-Norheim E, Svedenhag J, Ekblom B, Hjemdahl P (1985a) Co-release of neuropeptide Y and catecholamines during physical exercise in man. Biochem Biophys Res Commun 133: 30–36.PubMedCrossRefGoogle Scholar
  20. Lundberg JM, Torssell L, Sollevi L, Sollevi A, Pernow J, Theodorsson-Norheim E, Anggard A, Hamberger B (1985b) Neuropeptide Y and sympathetic vascular control in man. Regul Pept 13: 41–52.PubMedCrossRefGoogle Scholar
  21. Lundberg JM, Fried G, Pernow J, Theodorsson-Norheim E (1986a) Co-release of neuropeptide Y and catecholamines upon adrenal activation in the cat. Acta Physiol Scand 126: 231–238.PubMedCrossRefGoogle Scholar
  22. Lundberg JM, Hemsén A, Fried G, Theodorsson-Norheim E, Lagercrantz H (1986b) Co-release of neuropeptide Y (NPY)-like immunoreactivity and catecholamines in newborn infants. Acta Physiol Scand 126: 471–473.PubMedCrossRefGoogle Scholar
  23. Micalizzi ER, Pals DT (1979) Evaluation of plasma norepinephrine as an index of sympathetic neuron function in the conscious, unrestrained rat. Life Sci 24: 2071–2076.PubMedCrossRefGoogle Scholar
  24. Morris MJ, Russell AE, Kapoor V, Cain MD, Elliott JM, West MJ, Wing LMH, Chalmers JP (1986) Increases in plasma neuropeptide Y concentrations during sympathetic activation in man. J Auton Nerv Syst 17: 143–149.PubMedCrossRefGoogle Scholar
  25. Morris M, Kapoor V, Chalmers J (1987) Plasma neuropeptide Y concentration is increased after hemorrhage in concious rats: relative contributions of sympathetic nerves and the adrenal medulla. J Cardiovasc Pharmacol 9: 541–545.PubMedCrossRefGoogle Scholar
  26. Picotti GB, Carruba MO, Ravanzzani C, Cesura AM, Galva MD, Da Prada M (1979) Plasma catecholamines in rats exposed to cold: effects of ganglionic and adrenoreceptor blockade. Eur J Pharmacol 69: 321–329.CrossRefGoogle Scholar
  27. Potter EK (1988) Neuropeptide Y as an autonomic neurotransmitter. Pharmacol Ther 37: 251–273.PubMedCrossRefGoogle Scholar
  28. Rivet JM, Castagné V, Corder R, Gaillard R, Mormède P (1989) Study of the influence of stress and adrenalectomy on central and peripheral neuropeptide Y levels. Comparison with catecholamines. Neuroendocrinology 50: 413–420.PubMedCrossRefGoogle Scholar
  29. Rosak C, Vogel D, Althoff P-H, Neubauer M, Brecht H-M, Schöffling K (1982) Hormonal and metabolic parameters following insulin-induced hyperglycemia. Endokrinologie 79: 337–344.PubMedGoogle Scholar
  30. Rudehill A, Olcen M, Sollevi A, Hamberger B, Lundberg JM (1987) Release of neuropeptide Y upon haemorrhagic hypovolemia in relation to vasoconstrictor effects in the pig. Acta Physiol Scand 131: 517–523.PubMedCrossRefGoogle Scholar
  31. Sawchenko PE, Swanson LW, Grzanna R, Howe PRC, Bloom SR, Polak JM (1985) Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons. J Comp Neural 241: 138–153.CrossRefGoogle Scholar
  32. Schon F, Allen JM, Yeats JC, Kent A, Kelly JS, Bloom SR (1986) The effect of 6-hydroxydopamine, reserpine and cold stress on the neuropeptide Y content of the rat central nervous system. Neuroscience 19: 1247–1250.PubMedCrossRefGoogle Scholar
  33. Smythe GA, Bradshaw JE, Vining RF (1983) Hypothalamic monoamine control of stress-induced adrenocorticotropin release in the rat. Endocrinology 122: 1977–1983.Google Scholar
  34. Stjärne L, Lundberg JM, Astrand P (1986) Neuropeptide Y-a cotransmitter with nora-drenaline and adenosine 5′-triphosphate in the sympathetic nerves of the mouse vas deferens? A biochemical, physiological and electropharmacological study. Neuroscience 18: 151–166.PubMedCrossRefGoogle Scholar
  35. Szafarczyk A, Alonso G, Ixart G, Malaval F, Assenmacher I (1985) Diurnal-stimulated and stress-induced ACTH release in rats is mediated by ventral noradrenergic bundle. Am J Physiol; Endocr Metab 249: E219–E226.Google Scholar
  36. Takahashi K, Mouri T, Murakami O, Itoi K, Sone M, Ohneda M, Nozuki M, Yoshinaga K (1988) Increases of neuropeptide Y-like immunoreactivity in plasma during insulin-induced hypoglycemia in man. Peptides 9: 433–436.PubMedCrossRefGoogle Scholar
  37. Tatemoto K (1982) Neuropeptide Y: complete amino acid sequence of the brain peptide. Proc Natl Acad Sci USA 79: 5485–5489.PubMedCrossRefGoogle Scholar
  38. Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y—A novel peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296: 659–660.PubMedCrossRefGoogle Scholar
  39. Wahlestedt C, Skagerberg G, Ekman R, Heilig M, Sundler F, Hakanson R (1987) Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary-adrenocortical axis in the rat. Brain Res 417: 33–38.PubMedCrossRefGoogle Scholar
  40. Watson JD, Sury MRJ, Corder R, Carson R, Bouloux PM, Lowry PJ, Besser GM, Hinds CJ (1988) Plasma levels of neuropeptide Y (NPY) are increased in human sepsis but are unchanged during canine endotoxin shock despite raised catecholamine concentrations. J Endocrinol 116: 421–426.PubMedCrossRefGoogle Scholar
  41. Westfall TC, Carpentier S, Chen XC, Beinfeld MC, Naes L, Meldrum MJ (1987) Pre-junctional and postjunctional effects of neuropeptide Y at the noradrenergic neuroef-fector junction of the perfused mesenteric arterial bed of the rat. J Cardiovasc Pharmacol 10: 716–722.PubMedCrossRefGoogle Scholar
  42. Zukowska-Grojec Z, Konarska M, McCarty R (1988) Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats. Life Sci 42: 1615–1624.PubMedCrossRefGoogle Scholar
  43. Zukowska-Grojec Z, Vaz AC (1988) Role of neuropeptide Y (NPY) in cardiovascular responses to stress. Synapse 2: 293–298.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • P. Mormède
    • 1
    • 3
  • V. Castagné
    • 1
  • J.-M. Rivet
    • 1
  • R. Gaillard
    • 2
  • R. Corder
    • 2
  1. 1.Laboratoire de Psychobiologie des Comportements AdaptatifsINSERM U259-INRABordeauxFrance
  2. 2.Laboratoire de Neuroendocrinologie, Clinique MédicaleHôpital Cantonal UniversitaireGenèveSwitzerland
  3. 3.INRA-INSERM U 259Bordeaux CedexFrance

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