Neuropeptide Regulation of the Autonomic Nervous System

  • Marvin R. Brown
Part of the Hans Selye Symposia on Neuroendocrinology and Stress book series (HANS SELYE SYMP)


Integration and coordination of complex autonomic efferent responses are achieved through unique arrangements of neuroanatomic pathways that receive both intra- and extra-CNS (central nervous system) neural afferent information. Identification of numerous biologically-active peptides and their receptors in certain brain regions, and the demonstration of the ability of these peptides to modify autonomic nervous system (ANS) functions, have led to the speculation that they may play a role in the physiologic regulation of the ANS1.


Mean Arterial Pressure Autonomic Nervous System Gastric Acid Secretion Corticotropin Release Factor Plasma Epinephrine 
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  1. 1.
    Brown MR, Fisher LA. Brain peptides as intercellular messengers. Implications for medicine. JAMA 1984;251:1310–1315.PubMedCrossRefGoogle Scholar
  2. 2.
    Bloom FE, Battenberg EL, Rivier J, et al. Corticotropin releasing factor (CRF): immunoreactive neurons and fibers in rat hypothalamus. Regul Pept (Fayetteville) 1982;4:43–48.Google Scholar
  3. 3.
    Swanson LW, Sawchenko PE, Rivier J, et al. Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 1983;36:165–186.PubMedCrossRefGoogle Scholar
  4. 4.
    Britton DR, Koob GF, Rivier J, et al. Intraventricular corticotropin-releasing factor enhances behavioral effects of novelty. Life Sci 1982;31:363–367.PubMedCrossRefGoogle Scholar
  5. 5.
    Kalin NH. Behavioral effects of ovine corticotropin-releasing factor administered to rhesus monkeys. Fed Proc 1985;44:249–253.PubMedGoogle Scholar
  6. 6.
    Brown MR, Fisher LA, Rivier J, et al. Corticotropin-releasing factor: effects on the sympathetic nervous system and oxygen consumption. Life Sci 1982;30:207–210.PubMedCrossRefGoogle Scholar
  7. 7.
    Brown MR, Fisher LA, Spiess J, et al. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 1982;111:928–931.PubMedCrossRefGoogle Scholar
  8. 8.
    Kurosawa M, Sato A, Swenson RS, et al. Sympatho-adrenal medullary functions in response to intracerebroventricularly injected corticotropin-releasing factor in anesthetized rats. Brain Res 1986;367:250–257.PubMedCrossRefGoogle Scholar
  9. 9.
    Fisher LA, Rivier J, Rivier C, et al. Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats. Endocrinology 1982;110:2222–2224.PubMedCrossRefGoogle Scholar
  10. 10.
    Brown MR, Fisher LA. Corticotropin-releasing factor: effects on the autonomic nervous system and visceral systems. Fed Proc 1985;44:243–248.PubMedGoogle Scholar
  11. 11.
    Ono N, Lumpkin MD, Samson WK, et al. Intrahypothalamic action of corticotropin-releasing factor (CRF) to inhibit growth hormone and LH release in the rat. Life Sci 1984;35:1117–1123.PubMedCrossRefGoogle Scholar
  12. 12.
    Rivier C, Rivier J, Vale W. Stress-induced inhibition of reproductive functions: role of endogenous corticotropin-releasing factor. Science 1986:231:607–608.PubMedCrossRefGoogle Scholar
  13. 13.
    Rivier C, Vale W. Corticotropin-releasing factor (CRF) acts centrally to inhibit growth hormone secretion in the rat. Endocrinology 1984;114:2409–2411.PubMedCrossRefGoogle Scholar
  14. 14.
    Taché Y, Goto Y, Gunion M, et al. Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor. Science 1983;222:935–937.PubMedCrossRefGoogle Scholar
  15. 15.
    Lenz HJ, Hester SE, Brown MR. Corticotropin releasing factor: Mechanisms to inhibit gastric acid secretion in conscious dogs. J Clin Invest 1985;75:889–895.PubMedCrossRefGoogle Scholar
  16. 16.
    Brown M. Corticotropin releasing factor: central nervous system sites of action. Brain Res 1986;399:10–14.PubMedCrossRefGoogle Scholar
  17. 17.
    Fisher LA. Corticotropin releasing factor: effects on baroreflex control of heart rate. Soc Neurosci Abstr 1985; Abstract 11.Google Scholar
  18. 18.
    Brown MR, Fisher LA. Autonomic and cardiovascular effects of corticotropin releasing factor (CRF) in the spontaneously hypertensive rat (SHR). Soc Neurosci Abstr 1986; Abstract 12.Google Scholar
  19. 19.
    Plotsky PM, Vale W. Hemorrhage-induced secretion of corticotropin-releasing factor-like immunoreactivity into the rat hypophysial portal circulation and its inhibition by glucocorticoids. Endocrinology 1984;114:164–169.PubMedCrossRefGoogle Scholar
  20. 20.
    Merchenthaler I, Hynes MA, Vigh S, et al. Immunocytochemical localization of corticotropin releasing factor (CRF) in the rat spinal cord. Brain Res 1983;275:373–377.PubMedCrossRefGoogle Scholar
  21. 21.
    Brown MR, Fisher LA. Glucocorticoid suppression of the sympathetic nervous system and adrenal medulla. Life Sci 1986;39:1003–1012.PubMedCrossRefGoogle Scholar
  22. 22.
    Rivier J, Rivier C, Vale W. Synthetic competitive antagonists of corticotropin releasing factor: effect on ACTH secretion in the rat. Science 1984,224:889–891.PubMedCrossRefGoogle Scholar
  23. 23.
    Brown MR, Fisher LA, Webb V, et al. Corticotropin-releasing factor: a physiologic regulator of adrenal epinephrine secretion. Brain Res 1985;328:355–357.PubMedCrossRefGoogle Scholar
  24. 24.
    Brown MR, Gray TS, Fisher LA. Corticotropin-releasing factor receptor antagonist: effects on the autonomic nervous system and cardiovascular function. Regul Pept (Fayetteville) 1986;16:321–329.Google Scholar
  25. 25.
    Segal DS, Mandell AJ. Differential behavioral effects of hypothalamic polypeptides. In: The Thyroid Axis, Drugs, and Behavior. Prange AJ, Jr, ed. New York: Raven Press, 1974: p. 29–133.Google Scholar
  26. 26.
    Metcalf G, Dettmar PW. Is thyrotropin releasing hormone an endogenous ergotropic substance in the brain? Lancet 1981;1:586–589.PubMedCrossRefGoogle Scholar
  27. 27.
    Taché Y, Vale W, Brown M. Thyrotropin-releasing hormone—CNS action to stimulate gastric acid secretion. Nature 1980;287:149–151.PubMedCrossRefGoogle Scholar
  28. 28.
    Kato Y, Kanno T. Thyrotropin-releasing hormone injected intracerebroventricularly in the rat stimulates exocrine pancreatic secretion via the vagus nerve. Regul Pept (Fayetteville) 1983;7:347–356.Google Scholar
  29. 29.
    Brown MR. Thyrotropin releasing factor: a putative CNS regulator of the autonomic nervous system. Life Sci 1981;28:1789–1795.PubMedCrossRefGoogle Scholar
  30. 30.
    Tonoue T. Stimulation by thyrotropin-releasing hormone of vagal outflow to the thyroid gland. Regul Pept (Fayetteville) 1982;3:29–39.Google Scholar
  31. 31.
    Somiya H, Tonoue T. Neuropeptides as central integrators of autonomic nerve activity: effects of TRH, SRIF, VIP and bombesin on gastric and adrenal nerves. Regul Pept (Fayetteville) 1984;9:47–52.Google Scholar
  32. 32.
    Myers RD, Metcalf G, Rice JC. Identification by microinjection of TRH-sensitive sites in the cat’s brain stem that mediate respiratory, temperature and other autonomic changes. Brain Res 1977;126:105–115.PubMedCrossRefGoogle Scholar
  33. 33.
    Hedner J, Hedner T, Wessberg P, et al. Effects of TRH and TRH analogues on the central regulation of breathing in the rat. Acta Physiol Scand 1983;117:427–437.PubMedCrossRefGoogle Scholar
  34. 34.
    Koivusalo F, Paakkari I, Leppäluoto J, et al. The effect of centrally administered TRH on blood pressure, heart rate and ventilation in the rat. Acta Physiol Scand 1979;106:83–86.PubMedCrossRefGoogle Scholar
  35. 35.
    Diz DI, Jacobowitz DM. Cardiovascular effects produced by injections of thyrotropin-releasing hormone in specific preoptic and hypothalamic nuclei in the rat. Peptides 1984;5:801–808.PubMedCrossRefGoogle Scholar
  36. 36.
    Niewoehner DE, Levine AS, Morley JE. Central effects of neuropeptides on ventilation in the rat. Peptides 1983;4:277–281.PubMedCrossRefGoogle Scholar
  37. 37.
    Feuerstein G, Hassen AH, Faden AI. TRH: cardiovascular and sympathetic modulation in brain nuclei of the rat. Peptides 1983;4:617–620.PubMedCrossRefGoogle Scholar
  38. 38.
    Taché Y, Vale W, Rivier J, et al. Brain regulation of gastric secretion: influence of neuropeptides. Proc Natl Acad Sci USA 1980;77:5515–5519.PubMedCrossRefGoogle Scholar
  39. 39.
    Fisher LA, Brown MR. Bombesin-induced stimulation of cardiac parasympathetic innervation. Regul Pept (Fayetteville) 1984;8:335–343.Google Scholar
  40. 40.
    Tonoue T, Somiya H, Matsumoto H, et al. Evidence that endogenous thyrotropin-releasing hormone (TRH) may control vagal efferents to thyroid gland: neural inhibition by central administration of TRH antiserum. Regul Pept (Fayetteville) 1982;4:293–298.Google Scholar
  41. 41.
    Pfeiffer A, Feuerstein G, Kopin IJ, et al. Cardiovascular and respiratory effects of mu-, delta- and kappa-opiate agonists microinjected into the anterior hypothalamic brain area of awake rats. J Pharmacol Exp Ther 1983;225:735–741.PubMedGoogle Scholar
  42. 42.
    VanLoon GR, Appel NM, Ho D. Beta-endorphin-induced stimulation of central sympathetic outflow: beta-endorphin increases plasma concentrations of epinephrine, norepinephrine and dopamine in rats. Endocrinology 1981;109:46–53.CrossRefGoogle Scholar
  43. 43.
    Lang RE, Gaida W, Ganten D, et al. Neuropeptides and central blood pressure regulation. In: Central Cardiovascular Control. Basic and Clinical Aspects. Ganten D, Pfaff D, eds. New York: Springer-Verlag, 1983: p. 103–123.Google Scholar
  44. 44.
    Sitsen JM, VanRee JM, DeJong W. Cardiovascular and respiratory effects of beta-endorphin in anesthetized and conscious rats. J Cardiovasc Pharmacol 1982;4:883–888.PubMedCrossRefGoogle Scholar
  45. 45.
    Morley JE, Levine AS, Silvis SE. Endogenous opiates inhibit gastric acid secretion induced by central administration of thyrotropin-releasing hormone (TRH). Life Sci 1981;29:293–297.PubMedCrossRefGoogle Scholar
  46. 46.
    Lenz HJ, Brown MR. Central nervous system actions of β-endorphin on gastric acid secretion. Brain Res 1987;413:1–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Holaday JW, Faden AI. Naloxone reversal of endotoxin hypotension suggests a role of endorphins in shock. Nature 1978;275:450–451.PubMedCrossRefGoogle Scholar
  48. 48.
    Faden AI, Holaday JW. Opiate antagonists: a role in the treatment of hypovolemic shock. Science 1979;205:317–318.PubMedCrossRefGoogle Scholar
  49. 49.
    Garrong W. The brain renin angiotensin system. In: Brain Peptides. Krieger DT, Brownstein MJ, Martin JB, eds. New York: Wiley, 1983: p. 806–826.Google Scholar
  50. 50.
    Reid IA. Actions of angiotensin II on the brain: mechanisms and physiologic role. Am J Physiol 1984;246:F533-F543.PubMedGoogle Scholar
  51. 51.
    Bickerton RK, Buckley JP. Evidence for a central mechanism in angiotensin induced hypertension. Proc Soc Exp Biol Med 1961;106:834–836.Google Scholar
  52. 52.
    Ferrario CM, Gildenberg PL, McCubbin JW. Cardiovascular effects of angiotensin mediated by the central nervous system. Circ Res 1972;30:257–262.PubMedGoogle Scholar
  53. 53.
    Fisher LA, Brown MR. Corticotropin-releasing factor and angiotensin II: comparison of CNS actions to influence neuroendocrine and cardiovascular function. Brain Res 1984;296:41–47.PubMedCrossRefGoogle Scholar
  54. 54.
    Casto R, Phillips MI. Mechanism of pressor effects by angiotensin in the nucleus tractus solitarius of rats. Am J Physiol 1984;247:R575-R581.PubMedGoogle Scholar
  55. 55.
    Rettig R, Healy DP, Printz MP. Cardiovascular effects of microinjections of angiotensin II into the nucleus tractus solitarii. Brain Res 1986;364:233–240.PubMedCrossRefGoogle Scholar
  56. 56.
    Brown MR, Fisher LA. Brain peptide regulation of adrenal epinephrine secretion. Am J Physiol 1984;247:E41-E46.PubMedGoogle Scholar
  57. 57.
    Brown MR, Rivier C, Vale W. Central nervous system regulation of adrenocorticotropin secretion: role of somatostatins. Endocrinology 1984;114:1546–1549.PubMedCrossRefGoogle Scholar
  58. 58.
    Brown MR. Bombesin and somatostatin related peptides: effects on oxygen consumption. Brain Res 1982;242:243–246.PubMedCrossRefGoogle Scholar
  59. 59.
    Taché Y, Rivier J, Vale W, et al. Is somatostatin or a somatostatin-like peptide involved in central nervous system control of gastric secretion? Regul Pept (Fayetteville) 1981;1:307–315.Google Scholar
  60. 60.
    Brown M, Fisher L, Mason RT, et al. Neurobiological actions of cysteamine. Fed Proc 1985;44:2556–2560.PubMedGoogle Scholar
  61. 61.
    Walsh JH. Bombesin-like peptides. In: Brain Peptides. Krieger DT, Brownstein MJ, Martin JB, eds. New York: Wiley, 1983: p. 941–960.Google Scholar
  62. 62.
    Brown M, Märki W, Rivier J. Is gastrin releasing peptide mammalian bombesin? Life Sci 1980;27:125–128.PubMedCrossRefGoogle Scholar
  63. 63.
    Brown MR, Allen R, Fisher L. Bombesin alters the sympathetic nervous system response to cold exposure. Brain Res 1987;400:35–39.PubMedCrossRefGoogle Scholar
  64. 64.
    Brown MR. Central nervous system sites of action of bombesin and somatostatin to influence plasma epinephrine levels. Brain Res 1983;276:253–257.PubMedCrossRefGoogle Scholar
  65. 65.
    Gunion M, Taché Y. Bombesin microinfusion into the paraventricular nucleus suppresses gastric acid secretion. Brain Res; 1987; 422:118–128.PubMedCrossRefGoogle Scholar
  66. 66.
    O’Donohue TL, Chronwall BM, Pruss RM, et al. Neuropeptide Y and peptide YY neuronal and endocrine systems. Peptides 1985;6:755–768.PubMedCrossRefGoogle Scholar
  67. 67.
    Petty MA, Dietrich R, Lang RE. The cardiovascular effects of neuropeptide Y (NPY). Clin Exper Hypertens 1984;[A]6:1889–1892.CrossRefGoogle Scholar
  68. 68.
    Fuxe K, Agnati LF, Härfstrand A, et al. Central adminstration of neuropeptide Y induces hypotension, bradypnea and EEG synchronization in the rat. Acta Physiol Scand 1983;118:189–192.PubMedCrossRefGoogle Scholar
  69. 69.
    Carter DA, Vallejo M, Lightman SL. Cardiovascular effects of neuropeptide Y in the nucleus tractus solitarius of rats: relationship with noradrenaline and vasopressin. Peptides 1985;6:421–425.PubMedCrossRefGoogle Scholar
  70. 70.
    Vallejo M, Lightman SL. Pressor effect of centrally administered neuropeptide Y in rats: role of sympathetic nervous system and vasopressin. Life Sci 1986;38:1859–1866.PubMedCrossRefGoogle Scholar
  71. 71.
    Unger T, Becker H, Petty M, et al. Differential effects of central angiotensin II and substance P on sympathetic nerve activity in conscious rats. Circ Res 1985;56:563–575.PubMedGoogle Scholar
  72. 72.
    Unger T, Rascher W, Schuster C, et al. Central blood pressure effects of substance P and angiotensin II: role of the sympathetic nervous system and vasopressin. Eur J Pharmacol 1981;70:33–42.CrossRefGoogle Scholar
  73. 73.
    Iguchi A, Matsunaga H, Nomura T, et al. Glucoregulatory effects of intrahypothalamic injections of bombesin and other peptides. Endocrinology 1984;114:2242–2246.PubMedCrossRefGoogle Scholar
  74. 74.
    Keeler JR, Charlton CG, Helke CJ. Cardiovascular effects of spinal cord substance P: studies with a stable receptor agonist. J Pharmacol Exp Ther 1985;233:755–760.PubMedGoogle Scholar
  75. 75.
    Loewy AD, Sawyer WB. Substance P antagonist inhibits vasomotor responses elicited from ventral medulla in rat. Brain Res 1982;245:379–383.PubMedCrossRefGoogle Scholar
  76. 76.
    Takano Y, Martin JE, Leeman SE, et al. Substance P immunoreactivity released from rat spinal cord after kainic acid excitation of the ventral medulla oblongata: a correlation with increases in blood pressure. Brain Res 1984;291:168–172.PubMedCrossRefGoogle Scholar
  77. 77.
    Pittman QJ, Lawrence D, McLean L. Central effects of arginine vasopressin on blood pressure in rats. Endocrinology 1982;110:1058–1060.PubMedCrossRefGoogle Scholar
  78. 78.
    Riphagen CL, Bauce L, Veale WL, et al. The effects of intrathecal administration of arginine-vasopressin and substance P on blood pressure and adrenal secretion of epinephrine in rats. J Autonomic Nerv Syst 1986;16:91–99.CrossRefGoogle Scholar
  79. 79.
    Zerbe RL, Kirtland S, Faden AI, et al. Central cardiovascular effects of mammalian neurohypophyseal peptides in conscious rats. Peptides 1983;4:627–630.PubMedCrossRefGoogle Scholar
  80. 80.
    Zerbe RL, Feverstein G. Cardiovascular effects of centrally administered vasopressin in conscious and anesthetized rats. Neuropeptides 1985;6:471–484.PubMedCrossRefGoogle Scholar
  81. 81.
    Riphagen CL, Pittman QJ. Vasopressin influences renal function via a spinal action. Brain Res 1985;336:346–349.PubMedCrossRefGoogle Scholar
  82. 82.
    Fisher LA, Kikkawa DO, Rivier JE, et al. Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide. Nature 1983;305:534–536.PubMedCrossRefGoogle Scholar
  83. 83.
    Lenz HJ, Mortrud MT, Vale WW, et al. Calcitonin gene-related peptide acts within the central nervous system to inhibit gastric acid secretion. Regul Pept (Fayetteville) 1984;9:271–277.Google Scholar
  84. 84.
    Taché Y, Gunion M, Lauffenberger M, et al. Inhibition of gastric acid secretion by intracerebral injection of calcitonin gene related peptide in rats. Life Sci 1984;35:871–878.PubMedCrossRefGoogle Scholar
  85. 85.
    Hughes JJ, Levine AS, Morley JE, et al. Intraventricular calcitonin in gene-related peptide inhibits gastric acid secretion. Peptides 1984;5:665–667.PubMedCrossRefGoogle Scholar
  86. 86.
    Shults CW, Quiron R, Chronwall B, et al. A comparison of the anatomical distribution of substance P and substance P receptors in the rat central nervous system. Peptides 1984;5:1097–1128.PubMedCrossRefGoogle Scholar

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© Springer-Verlag New York Inc. 1989

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  • Marvin R. Brown

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