Vasopressin, the Blood-Brain Barrier, and Brain Performance

  • A. Ermisch
  • R. Landgraf
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 274)


For about a quarter of a century, nonapeptides of the vasopressin (VP) type, especially arginine-VP (AVP) and oxytocin (OXT), have been studied in relation to the behavioral performance of mammals. The starting point was the observation that, in addition to their classical roles in endocrine function, certain peptides modified central neuronal processes. The results of de Wied (1,2) attracted special interest, because they suggested the involvement of nonapeptides in learning and memory processes.


Atrial Natriuretic Factor Orotic Acid Brain Performance Peptide Molecule Large Neutral Amino Acid 
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  1. 1.
    de Wied, D., The influence of the posterior and intermediate lobe of the pituitary and pituitary peptides on the maintenance of a conditioned avoidance response in rats, Int J Neuropharmacol 4157–167,1965.CrossRefGoogle Scholar
  2. 2.
    de Wied, D., and B. Bohus, Long term and short term effects on retention of a conditioned avoidance response in rats by treatment with long acting pitresin and a-MSH, Nature 212 1484–1486, 1966.PubMedCrossRefGoogle Scholar
  3. 3.
    Sterba, G., and J. Kormann, Der einfluss von Oxytocinen auf das ständige hirnpotential von narkotisierten fröschen, Pflügers Archiv fur die Gesamte Physiologe 287 345–350, 1966.CrossRefGoogle Scholar
  4. 4.
    Schäker, W., F. Klingberg, G. Sterba, and L. Pickenhain, Der einfluss von oxytocin auf zentralnervöse funktionen bei der ratte im chronischen experiment, Pflügers Archiv fur die Gesamte Physiologie 288 322–331, 1966.CrossRefGoogle Scholar
  5. 5.
    Sterba, G., Ascending neurosecretory pathways of the peptidergic type, In F. Knowles and L. Vollrath (eds) Neurosecretion-The Final Neuroendocrine Pathway ,Springer Verlag, Berlin, pp. 38–47, 1974.Google Scholar
  6. 6.
    Sterba, G., Das oxytocinerge neurosekreterische system der Wirbeltiere, beitrag zu einem erweiterten konsept, Zool Jb Physiol 78 409–423, 1974.Google Scholar
  7. 7.
    Sterba, G., H. Petter, R. Landgraf, W. Lösecke, K. Sciler, W. Naumann, Cytochemistry of neurosecretory cells, In P.M. Gross (ed) Circumventricular Organs and Body Fluids, Vol III ,CRC Press, Inc., Boca Raton, pp. 63–82, 1987.Google Scholar
  8. 8.
    Sterba, G., G. Hoheisel, R. Wegelin, W. Naumann, and F. Schober, Peptide containing vesicles within neuro-neuronal synapses, Brain Res 169 55–64, 1979.PubMedCrossRefGoogle Scholar
  9. 9.
    de Wied, D., Neuropeptides and behaviour, In M.J. Parnham and J. Bruinvles (eds) Discoveries in Pharmacology, Volume 1 Psycho-and Neuro-Pharmacology ,Elsevier Science Publishers, B.V., Amsterdam, pp. 307–353, 1983.Google Scholar
  10. 10.
    Buijs, R.M., Vasopressin localization and putative functions in the brain, In D.M. Gash and G.J. Boer (eds) Vasopressin, Principles and Properties ,Plenum Press, New York, pp. 91–115, 1987.Google Scholar
  11. 11.
    Jard, S., Vasopressin isoreceptors in mammals relation to cyclic AMP-dependent and cyclic AMP-independent transduction mechanisms, In A. Kleinzeller and B.R. Martin (eds) Current Topics in Membranes and Transport, Volume 18 Membrane Receptors ,Academic Press, New York, pp. 255–285, 1983.Google Scholar
  12. 12.
    Kretzschmar, R., and A. Ermisch, Arginine-vasopressin binding to isolated hippocampal microvessels of rats with different endogenous concentrations of the neuropeptide, Exp Clin Endocrinol 94 151–156, 1989.PubMedCrossRefGoogle Scholar
  13. 13.
    Van Leeuwen, F.W., Vasopressin receptors in the brain and pituitary, In D.M. Gash and G.J. Boer (eds) Vasopressin, Principles and Properties ,Plenum Press, New York, pp. 477–496, 1987.Google Scholar
  14. 14.
    Poulain, DA., and D.T. Theodosis, Coupling of electrical activity and hormone release in mammalian neurosecretory neurons, Curr Top Neuroendocrinol 9 73–104, 1988.CrossRefGoogle Scholar
  15. 15.
    Jójárt, I., F. Joó, L. Siklós, FA. Lázló, Immunoelectronhistochemical evidence for innervation of brain microvessels by vasopressin-immunoreactive neurons in the rat, Neurosci Lett 51 259–264, 1984.PubMedCrossRefGoogle Scholar
  16. 16.
    Landgraf, R., I. Neumann, and H. Schwarzberg, Central and peripheral release of vasopressin and oxytocin in the conscious rat after osmotic stimulation, Brain Res 457 219–225, 1988.PubMedCrossRefGoogle Scholar
  17. 17.
    Demotes-Mainard, J., J. Chauveau, F. Rodrigues, J.D. Vincent, and DA. Poulain, Septal release of vasopressin in response to osmotic, hypovolemic and electrical stimulation in rats, Brain Res 381314–321, 1986.PubMedCrossRefGoogle Scholar
  18. Landgraf, R., T.J. Malkinson, T. Horn, W.L. Veale, K. Lederis, and Q.J. Pittman, Release of vasopressin and oxytocin from nucleus tractus solitarius/dorsal vagal nucleus following PVN stimulation in rats, Am J Physiol In Press.Google Scholar
  19. 19.
    Neumann, I., H. Schwarzberg, and R. Landgraf, Measurement of septal release of vasopressin and oxytocin by the push-pull technique following electrical stimulation of the paraventricular nucleus of rats, Brain Res 462 181–184, 1988.PubMedCrossRefGoogle Scholar
  20. Landgraf, R., T.J. Malkinson, W.L. Veale, K. Lederis, and Q.J. Pittman, Vasopressin and oxytocin in the rat brain in response to prostaglandin fever, In Preparation.Google Scholar
  21. 21.
    Pittman, Q.J., A. Naylor, P. Poulin, J. Disturnal, W.L. Veale, S.M. Martin, T.J. Malkinson, and B. Mathieson, The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders, Brain Res Bull 20 887–892, 1988.PubMedCrossRefGoogle Scholar
  22. 22.
    Neumann, I., R. Landgraf, Septal and hippocampal release of oxytocin, but not vasopressin, in the conscious lactating rat during suckling, J Neuroendocrinol 1 305–308, 1989.PubMedCrossRefGoogle Scholar
  23. 23.
    Kasting, N.W., Potent stimuli for vasopressin release, hypertonic saline and hemorrhage cause antipyresis in the rat, Regul Pept 15 293–300, 1986.PubMedCrossRefGoogle Scholar
  24. 24.
    Koob, G.F., R. Dantzer, F. Rodriguez, F.E. Bloom, and M. Le Moal, Osmotic stress mimics effects of vasopressin on learned behaviour, Nature 315 750–752, 1985.PubMedCrossRefGoogle Scholar
  25. 25.
    Pittman, Q. J., and L.G. Franklin, Vasopressin antagonist in nucleus tractus solitarius/vagal area reduces pressor and tachycardia responses to paraventricular nucleus stimulation in rats, Neurosci Lett 56 155–160, 1985.PubMedCrossRefGoogle Scholar
  26. 26.
    Kasting, N.W., Criteria for establishing a physiological role for brain peptides. A case in point the role of vasopressin in thermoregulation during fever and antipyresis, Brain Res Rev 14 143–153, 1989.PubMedCrossRefGoogle Scholar
  27. 27.
    Doris, P.A., Central cardiovascular regulation and the role of vasopressin a review, Clin Exp Theor Practice A6 2197–2217, 1984.CrossRefGoogle Scholar
  28. 28.
    Schmid, P.G., F.M. Sharabi, G.B. Guo, F.M. Abboud, and M.D. Thanes, Vasopressin and oxytocin in the neural control of the circulation, Fed Proc 43 97–102, 1984.PubMedGoogle Scholar
  29. 29.
    Leibowitz, S.F., Hypothalamic paraventricular nucleus interaction between α2-noradrenergic system and circulating hormones and nutrients in relation to energy balance, Neurosci Biobehav Rev 12 101–109, 1988.PubMedCrossRefGoogle Scholar
  30. 30.
    Messing, R.B., S.B. Sparker, Greater task difficulty amplifies the facilitatory effect of des-glycinamide arginine vasopressin on appetitivily motivated learning, Behav Neurosci 99 1114–1119, 1985.PubMedCrossRefGoogle Scholar
  31. 31.
    Berkowitz, BA., S. Sherman, Characterization of vasopressin analgesia, J Pharmacol Exp Ther 220 329–334, 1982.PubMedGoogle Scholar
  32. 32.
    Ermisch, A., M. Koch, and T. Barth, Learning performance of rats after pre-and postnatal application of arginine-vasopressin, In G. Dörner, S.M. McCann, and L. Martini (eds) Monographs in Neural Sciences, Volume 12, Systemic Hormones, Neurotransmitters and Brain Development ,Karger, Basel, pp. 142–147, 1985.Google Scholar
  33. 33.
    Ermisch, A., R. Landgraf, and P. Möbius, Vasopressin and oxytocin in brain areas of rats with high or low behavioral performance, Brain Res 379 24–29, 1986.PubMedCrossRefGoogle Scholar
  34. 34.
    Ermisch, A., R. Landgraf, P. Möbius, and H. Petter, Behavioral performance of rats and the content of vasopressin and oxytocin in distinct brain areas, In H. Matthies (ed) Learning and Memory Mechanisms of Information Storage in the Nervous System, Advances in the Biosciences, Volume 59 ,Pergamon Press, Oxford, pp. 369–372, 1986.Google Scholar
  35. 35.
    Landgraf, R, Simultaneous measurement of arginine vasopressin and oxytocin in plasma and neurohypophyses by radioimmunoassay, Endokrinologie 78 191–204, 1981.PubMedGoogle Scholar
  36. 36.
    Hasche, W., Grundzüge der neurophysiologie unter dem aspekt der integrativen Tätikeit des ZNS, 3. Aufl., VEB Gustav Fischer Verlag, Jena, 1986.Google Scholar
  37. 37.
    Melander, T., WA. Staines, T. Hökfelt, A. Rökaeus, F. Eckenstein, P.M. Salvaterr, and B.H. Wainer, Galanin-like immunoreactivity in cholinergic neurons of the septum-basal forebrain complex projection to the hippocampus of the rat, Brain Res 360 130–138, 1985.PubMedCrossRefGoogle Scholar
  38. 38.
    Nyakas, C, P.G.M. Luiten, D.G. Spencer, and J. Traper, Detailed projection patterns of the septal and diagonal band efferents to the hippocampus in the rat with emphasis on innervation of CA1 and dentate gyrus, Brain Res Bull 18 533–545, 1987.PubMedCrossRefGoogle Scholar
  39. 39.
    Kennedy, M.B., Synaptic memory molecules, Nature 335 770–772, 1988.PubMedCrossRefGoogle Scholar
  40. 40.
    Matthies, H., Plasticity in the nervous system an approach to memory research, In CA. Marsan and H. Matthies (eds) Neuronal Plasticity and Memory Formation, IBRO-Monograph Series Volume 9 ,Raven Press, New York, pp. 1–15, 1982.Google Scholar
  41. 41.
    Rose, S.P.R., Obstacles and progress in studying the cell biology of learning and memory, In H. Matthies (ed) Learning and Memory Mechanisms of Information Storage in the Nervous System, Advances in the Biosciences Volume 59 ,Pergamon Press, Oxford, pp. 165–172, 1986.Google Scholar
  42. 42.
    Zlokovič, B.V., D.J. Begley, M.B. Segal, H. Davson, L.J. Rakič, M.N. Lipovač, D.M. Mitrovič, and R.M. Jankov, Neuropeptide transport mechanisms in the central nervous system, In L.J. Rakič, DJ. Begley, H. Davson, and B.V. Zlokovič (eds) Peptide and Amino Acid Transport Mechanisms in the Central Nervous System ,Stockton Press, NY, pp. 3–20, 1988.Google Scholar
  43. 43.
    Oldendorf, W.H., Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard, Brain Res 24 372–376, 1970.PubMedCrossRefGoogle Scholar
  44. 44.
    Reith, J., A. Ermisch, N.H. Diemer, and A. Gjedde, Saturable retention of vasopressin by hippocampus vessels in vivo, associated with inhibition of blood-brain barrier transfer of large neutral amino acids, J Neurochem 49 1471–1479, 1987.PubMedCrossRefGoogle Scholar
  45. 45.
    Jod, F., The blood-brain barrier new aspects to the function of the cerebral endothelium, Nature 321 197–198, 1986.CrossRefGoogle Scholar
  46. 46.
    Oldendorf, W.H., and L.D. Braun, [3H]tryptamine and [3H]-water as diffusible internal standards for measuring brain extraction of radio-labeled substances following carotid injection, Brain Res 113219–224, 1976.PubMedCrossRefGoogle Scholar
  47. 47.
    Rapoport, S.I., WA. Klee, K.D. Pettigrew, and K. Ohno, Entry of opioid peptides into the central nervous system, Science 207 84–86, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    Frank, H.J.L., and W.M. Pardridge, A direct in vitro demonstration of insulin binding to isolated brain microvessels, Diabetes 30 757–761, 1981.PubMedCrossRefGoogle Scholar
  49. 49.
    Kretzschmar, R., R. Landgraf, A. Gjedde, and A. Ermisch, Vasopressin binds to microvessels from rat hippocampus, Brain Res 380 325–330, 1986.PubMedCrossRefGoogle Scholar
  50. 50.
    Speth, R.C., and S.I. Harik, Angiotensin II receptor binding sites in brain microvessels, Proc Natl Acad Sci USA 82 6340–6343, 1985.PubMedCrossRefGoogle Scholar
  51. 51.
    Chabrier, P.E., P. Roubert, P. Plas, and P. Braquet, Blood-brain barrier and atrial natriuretic factor, Can J Physiol Pharmacol 66 276–279, 1988.PubMedCrossRefGoogle Scholar
  52. 52.
    Smith, K.R., A. Kato, and R.T. Borchardt, Characterization of specific receptors for atrial natriuretic factor on cultured bovine brain capillary endothelial cells, Biochem Biophys Res Comm 157 308–314, 1988.PubMedCrossRefGoogle Scholar
  53. 53.
    Niwa, M., M. Ibaragi, K. Tsutsumi, M. Kurihara, A. Himeno, K. Mori, and M. Ozaki, Specific atrial natriuretic peptide binding sites in rat cerebral capillaries, Neurosci Lett 91 89–94, 1988.PubMedCrossRefGoogle Scholar
  54. 54.
    Cornford, E.M., The blood-brain barrier, a dynamic regulatory interface, Mol Physiol 7 219–260,1985.Google Scholar
  55. 55.
    Van Zwieten, E.J., R. Ravid, D.F. Swaab, and T.J. Woude, Immunocytochemically stained vasopressin binding sites on blood vessels in the rat brain, Brain Res 474 369–373, 1988.PubMedCrossRefGoogle Scholar
  56. 56.
    Ermisch, A., Blood-brain barrier and peptides, Wiss Z Karl-Marx-Univ Leipzig Math-Naturwiss Reihe 36 72–77, 1987.Google Scholar
  57. 57.
    Möhring, B., and J. Möhring, Plasma ADH in normal Long-Evans rats and in Long-Evans rats heterozygous and homozygous for hypothalamic diabetes insipidus, Life Sci 17 1307–1314, 1975.PubMedCrossRefGoogle Scholar
  58. 58.
    Hess, J., A. Gjedde, and H. Jessen, Vasopressin receptors at the blood-brain barrier in rats, Wizz Z Karl-Marx-Univ Leipzig Math-Naturwiss Reihe 36 81–83, 1987.Google Scholar
  59. 59.
    Ermisch, A., R. Landgraf, P. Brust, R. Kretzschmar, and J. Hess, Peptide receptors of the cerebral capillary endothelium and the transport of amino acids across the blood-brain barrier, In L.J. Rakič, D.J. Begley, H. Davson, and B.V. Zlokovič (eds) Peptide and Amino Acid Transport Mechanisms in the Central Nervous System, Stockton Press, New York, pp. 41–54, 1988.Google Scholar
  60. 60.
    Landgraf, R., J. Hess, and E. Hartmann, The influence of oxytocin on the regional uptake of [3H] orotic acid by rat brain, Endokrinologie 70 45–52, 1977.PubMedGoogle Scholar
  61. 61.
    Landgraf, R., J. Hess, and A. Ermisch, The influence of vasopressin on the regional uptake of [3H] orotic acid by rat brain, Acta Biol Med Germ 37 655–658, 1978.PubMedGoogle Scholar
  62. 62.
    Ermisch, A., T. Barth, HJ. Rühle, J. Skopková, P. Hrbas, and R. Landgraf, On the blood-brain barrier to peptides accumulation of labelled vasopressin, desglyHG2-vasopressin and oxytocin by brain regions, Endocrinologia Experimentalis 19 29–37, 1985.PubMedGoogle Scholar
  63. 63.
    Brust, P., Changes in regional blood-brain transfer of L-leucine elicited by arginine-vasopressin, J Neurochem 46 534–541, 1986.PubMedCrossRefGoogle Scholar
  64. 64.
    Brust, P., and J. Zicha, Kinetics of regional blood-brain barrier transport of L-leucine in Brattleboro rats, Biomed Biochim Acta 47 1013–1021, 1988.PubMedGoogle Scholar
  65. 65.
    Ermisch, A., H.-J. Rühle, K. Neubert, K. Hartrodt, and R. Landgraf, On the blood-brain barrier to peptides [3H]β-casomorphin-5 uptake by eighteen brain regions in vivo, J Neurochem 41 1229–1233, 1983.PubMedCrossRefGoogle Scholar
  66. 66.
    Ermisch, A., H.-J. Rühle, R. Landgraf, and J. Hess, Blood-brain barrier and peptides, J Cereb Blood Flow Metab 5 350–357, 1985.PubMedCrossRefGoogle Scholar
  67. 67.
    Landgraf, R., E. Klauschenz, M. Bienert, A. Ermisch, and P. Oehme, Some observations indicating a low brain uptake of [3H]Nle11 -substance P, Pharmazie 38 108–110, 1983.PubMedGoogle Scholar
  68. 68.
    Gjedde, A., and M. Rasmussen, Blood-brain glucose transport in the conscious rat comparison of the intravenous and intracarotid injection methods, J Neurochem 35 1375–1381,1980.PubMedCrossRefGoogle Scholar
  69. 69.
    Kretzschmar, R., and A. Ermisch, Arginine-vasopressin binding to isolated cerebral microvessels, Wiss Z Karl-Marx-Univ Leipzig Math-Naturwiss Reihe 36 78–80,1987.Google Scholar
  70. 70.
    Pearlmutter, A.F., M. Szkrybalo, Y. Kim, and S.I. Harik, Arginine vasopressin receptors in pig cerebral microvessels, cerebral cortex and hippocampus, Neurosci Lett 87 121–126, 1988.Google Scholar
  71. 71.
    Chabrier, P.E., P. Roubert, and P. Braquet, Specific binding of atrial natriuretic factor in brain microvessels, Proc Natl Acad Sci USA 84 2078–2081,1987.PubMedCrossRefGoogle Scholar
  72. 72.
    Pillion, DJ., J.F. Haskell, and E. Meezan, Cerebral cortical microvessels an insulin-sensitive tissue, Biochem Biophys Res Comm 104 686–692, 1982.PubMedCrossRefGoogle Scholar
  73. 73.
    Haskell, J.F., E. Meezan, and DJ. Pillion, Identification of the insulin receptor of cerebral microvessels, Am J Physiol 248 E115–E125, 1985.PubMedGoogle Scholar
  74. 74.
    Frank, HJ.L, T. Jankovic-Vokes, W.M. Pardridge, and W.L. Morris, Enhanced insulin binding to blood-brain barrier in vivo and to brain microvessels in vitro in newborn rabbits, Diabetes 34 728–733, 1985.PubMedCrossRefGoogle Scholar
  75. 75.
    Pardridge, W.M., J. Eisenberg, and J. Yang, Human blood-brain barrier insulin receptor, J Neurochem 44 1771–1778, 1985.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • A. Ermisch
    • 1
  • R. Landgraf
    • 1
  1. 1.Department of Cell Biology and Regulation Section of Biosciences and Interdisciplinary Centre of NeurosciencesKarl Marx UniversityLeipzigGDR

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