Peptides and Proteins

  • Hugh Davson
  • Berislav Zloković
  • Ljubisa Rakić
  • Malcolm B. Segal


Peptides are short chains of amino acids containing, usually, less than 50–100 residues linked by peptide bonds. A number of peptides have been shown to exist in the cell bodies, as well as in the axons and nerve terminals, of the central nervous system and, by definition, these are called brain peptides or neuropeptides. Neuropeptides have been identified in different brain regions, and neuronal peptidergic pathways have been visualized and characterized in the central nervous system by means of different immunocytochemical, immunofluorescence and radioreceptor assay techniques. For most brain peptides, the localization of their neuronal pathways has been one of the most powerful tools in the understanding of their functions.


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  1. Abbott, J., Butt, A.M. and Zloković, B.V. (1988). Techniques for study of blood-brain barrier in non-mammalian species. In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 293–397Google Scholar
  2. Adam, G., Joó, F., Temesvari, P., Dux, E. and Szerdahelyi, P. (1988). Effects of acute hypoxia on the adenylate cyclase activity and albumin transport of brain microvessels. Neurochem. Int. (in press)Google Scholar
  3. Akmal, M.D., Goldstein, A., Multani, S. and Massry, S.G. (1984). Role of uremia, brain calcium and parathyroid hormone on changes in electroencephalogram in chronic renal failure. Am. J. Physiol., 246, F575–F579Google Scholar
  4. Aldred, A.R., Dickson, P.W., Marley, P.D. and Schreiber, G. (1987). Distribution of transferrin synthesis in brain and other tissues in the rat. J. Biol. Chem., 262, 5293–5297PubMedGoogle Scholar
  5. Banks, W.A. and Kastin, A.J. (1983). CSF-plasma relationships for DSIP and some other neuropeptides. Pharmacol. Biochem. Behav., 19, 1037–1040CrossRefPubMedGoogle Scholar
  6. Banks, W.A. and Kastin, A.J. (1985). Aluminium alters blood-brain barrier permeability to non-peptides. Neuropharmacology, 24, 407–412CrossRefGoogle Scholar
  7. Banks, W.A. and Kastin, A.J. (1986a). Aging, peptides and the blood-brain barrier: implications and speculations. In Crook, T., Bartus, R., Ferris, S. and Gerhson, S.M. (Eds), Treatment Development Strategies for Alzheimers Disease. Powley Associates, Madison, Conn., pp. 245–265Google Scholar
  8. Banks, W.A. and Kastin, A.J. (1989b). Modulation of the carrier-mediated transport of Tyr-MIF-1 across the blood-brain barrier by essential amino acids. J. Pharmacol., 239, 668–672Google Scholar
  9. Banks, W.A. and Kastin, A.J. (1988a). Peptides and the blood-brain barrier. In Rakić, Lj., Begley, Dj., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 21–32CrossRefGoogle Scholar
  10. Banks, W.A. and Kastin, A.J. (1988b). Twenty-one hormones fail to inhibit the brain to blood transport system for Tyr-MIF-1 and the enkephalins in mice. J. Pharm. Pharmacol., 40, 289–291CrossRefPubMedGoogle Scholar
  11. Banks, W.A., Kastin, A.J. and Coy, D.H. (1983). Delta sleep-inducing peptide (DSIP)-like materials absorbed by the gastrointestinal tract of the neonatal rat. Life Sci., 33, 1587–1897CrossRefPubMedGoogle Scholar
  12. Banks, W.A., Kastin, A.J., Fishman, A.J., Coy, D.H. and Strauss, S.L. (1986). Carrier mediated transport of enkephalins and N-Tyr-MIF-1 across the blood-brain barrier. Am. J. Physiol., 251 (Endocrinol. Metab., 14), E477—E482Google Scholar
  13. Banks, W.A., Kastin, A.J., Horvath, A. and Michals, E.A. (1987). Carrier-mediated transport of vasopressin across the blood-brain barrier of the mouse. J. Neurosci. Res., 18, 326–332CrossRefPubMedGoogle Scholar
  14. Banks, W.A., Kastin, A.J. and Nager, B.J. (1988). Analgesia and the blood-brain barrier transport system for Tyr-MIF-1 enkephalin: evidence for dissociation. Neuropharmaco-logy, 27, 175–179CrossRefGoogle Scholar
  15. Banks, W.A., Kastin, A.J. and Siznick, J.K. (1985). Modulation of inununoactive levels of DSIP and blood-brain barrier permeability by lighting and diurnal rhythm. J. Neurosci. Res., 14, 347–355CrossRefPubMedGoogle Scholar
  16. Bar, R.S., DeRose, A., Sandra, A., Peacock, M.L. and Owen, W.G. (1983). Insulin binding to microvascular endothelium of intact heart: a kinetic and morphometric analysis. Am. J. Physiol., 244, E447–E543Google Scholar
  17. Barrera, C.M., Kastin, A.J. and Banks, W.A. (1987). D-[Ala1]-Peptide T amide is transported from blood to brain by a saturable system. , 19, 629–633Google Scholar
  18. Barry, D.I., Paulson, O.B. and Hertz, M.M. (1980). The blood-brain barrier: an overview with special reference to insulin effect on glucose transport. Acta Neurol. Scand., 778, 147–156Google Scholar
  19. Baskin, D.G., Dorsa, D.M., Figlewicz, D.P., Corp, E.S., Wilcox, B.J., Wallum, B.J. and Woods, S.C. (1988). Insulin as a regulatory peptide in the CNS. In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 79–90CrossRefGoogle Scholar
  20. Baskin, D.G., Figlewicz, D.P., Woods, S.C., Porte, D. and Dorsa, D.M. (1987). Insulin in the brain. Ann. Rev. Physiol., 49, 335–347CrossRefGoogle Scholar
  21. Baskin, D.G., Woods, S.C., West, D.B., van Houten, M., Posner, B.I., Dorsa, D.M. and Porte, D. Jr. (1983). Immunocytochemical detection of insulin in rat hypothalamus and its possible uptake from cerebrospinal fluid. Endocrinology, 112, 1818–1825CrossRefGoogle Scholar
  22. Bayliss, W.M. and Starling, E.H. (1902). The mechanism of pancreatic secretion, J. Physiol, 28, 325–353CrossRefGoogle Scholar
  23. Beckwith, B.E., Couk, D.I. and Till, T.S. (1983). Vasopressin analog influences the performance of males on a reaction time task. Peptides, 4, 707–709CrossRefGoogle Scholar
  24. Begley, D.J. and Chain, D.G. (1982). Clearance of glutamic acid, glutamine and pyroglutamic acid from the cerebrospinal fluid of the rabbit: a comparison with thyrotropin releasing hormone. J. Physiol., 326, 22–23Google Scholar
  25. Begley, D.J. and Chain, D.G. (1988). Transport of encephalin from cerebrospinal fluid of the rabbit. In Rakić, Lj., Begley, D.G., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 55–64CrossRefGoogle Scholar
  26. Begley, D.J., Michaelson, I.A. and Davson, H. (1980). Clearance of the dipeptide glycyl-L-leucine from rabbit cerebrospinal fluid. J. Physiol., 307, 83PGoogle Scholar
  27. Begley, D.J., Squires, L.K., Zloković, B.V. and Mitrović, D.M. (1990). Permeability of blood-brain barrier to the immuno-suppressive cyclic peptide cyclosporin A. J. Neurochem., 55, 1222–1230CrossRefPubMedGoogle Scholar
  28. Begley, J.D. and Zloković, B.V. (1986). Neuropeptides and the blood-brain barrier. In Suckling, A.J., Rumsby, M.G. and Bradbury, M.W. (Eds), Blood-Brain Barrier in Health and Disease. Verlagsgesellschaft, Weinheim, 98–108Google Scholar
  29. Ben-Jonathan, N., Mical, R.S. and Porter, J.C. (1974). Transport of LRF from CSF to hypophysial portal systemic blood and the release of LH. Endocrinology, 95, 18–25CrossRefGoogle Scholar
  30. Bloom, F.E. (1987). Molecular diversity and cellular functions of neuropeptides. In de Kloet, E.R., Wiegant, A.M. and de Wied, D. (Eds), Neuropeptides and Brain Function. Progress in Brain Research, Vol. 72, pp. 213–223CrossRefGoogle Scholar
  31. Boyles, J.K., Pitas, R.E., Wilson, E., Mahley, R.W. and Taylor, J.M. (1985). Apolipopro-tein, E: associated with astrocytic glia of the central nervous system and with non-myelinating glia of the peripheral nervous system. J. Clin. Invest., 76, 1501CrossRefPubMedPubMedCentralGoogle Scholar
  32. Bradbury, W.B. (1989). Transport across the blood-brain barrier. In Neuwelt, E.A. (Ed.), Implications of the Blood-Brain Barrier and Its Manipulation. Plenum Medical Book Company. New York. pp. 119–137CrossRefGoogle Scholar
  33. Brightman, M.W. and Reese, T.S. (1969). Junctions between intimately opposed cell membranes in the vertebrate brain. J. Cell Biol., 40, 648–677CrossRefPubMedPubMedCentralGoogle Scholar
  34. Broadwell, R.D., Balin, B.J. and Salcman, M. (1988). Transcytotic pathway for blood-borne protein through the blood-brain barrier. Proc. Natl Acad. Sci. USA. 85. 632–636CrossRefPubMedPubMedCentralGoogle Scholar
  35. Broadwell, R.D., Balin, B.J., Salcman, M. and Kaplan, R.S. (1983). Brain-blood barrier? Yes and no. Proc. Natl. Acad Sci. USA, 80 7352–7356CrossRefGoogle Scholar
  36. Buijs, R.M. and Van Heerikhuize, J.J. (1982). Vasopressin and oxytocin release in the brain-a synaptic event. Brain Res., 252, 71–76CrossRefPubMedGoogle Scholar
  37. Burbach, J.P., Kovacs, G.L., De Wied, D., van Nispen, J.W. and Greven, H.M. (1983). A major metabolite of arginine vasopressin in the brain is a highly potent neuropeptide. Science, 221, 1310–1312CrossRefGoogle Scholar
  38. Cefalu, W.T. and Pardridge, W.M. (1985). Restrictive transport of a lipid-soluble peptide (cyclosporin) through the blood–brain barrier. J. Neurochem., 45, 1954–1956CrossRefPubMedGoogle Scholar
  39. Coghlan, J.P., Congiu, M., Denton, D.A., Fei, D.T. and Park, R.G. (1986). Augmented plasma renin levels in dehydrated sheep with periventricular lesions. Brain Res., 376, 416–419CrossRefPubMedGoogle Scholar
  40. Cohen, S.L., Knight, M., Tamminga, C.A. and Chase, T.N. (1983). Tolerance to the antiavoidance properties of cholecystokinin-octapeptide. Peptides, 4, 67–70CrossRefGoogle Scholar
  41. Congiu, M., Denton, D.A., Park, R.G., Penschow, J., Simpson, J.B., Tarjan, E., Weisinger, R.S. and Wright, R.D. (1984). The anterior wall of the third cerebral ventricle and homeostatic responses to dehydration. J. Physiol. (Paris), 79, 421–427Google Scholar
  42. Connelly, J.C., Skidgel, R.A., Schulz, W.W., Johnson, A.R. and Erdos E.G. (1985). Neutral endopeptidase 24.11 in human neutrophils: cleavage of chemotactic peptide. Proc. Natl Acad. Sci. USA, 82, 8737–8741CrossRefGoogle Scholar
  43. Cornford, E.M., Braun, L.D., Crane, P.D. and Oldendorf, W.H. (1978). Blood-brain barrier restrictions of peptides and the low uptake of enkephalins. Endocrinology, 103, 1297–1303CrossRefGoogle Scholar
  44. Corp, E.S., Woods, S.C., Porte, D., Jr., Dorsa, D.M., Figlewicz, D.P. and Baskin, D.G. (1986). Localization of I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci. Lett., 70, 17–22CrossRefPubMedGoogle Scholar
  45. Davis, J.L. and Pico, R.M. (1984). Arginine vasotocin delays extinction of a conditioned avoidance behavior in neonatal chicks. Peptides, 5, 1221–1223CrossRefGoogle Scholar
  46. Davson, H. (1955). A comparative study of the aqueous humor and cerebrospinal fluid in the rabbit. J. Physiol., 129, 11–133CrossRefGoogle Scholar
  47. Davson, H. and Oldendorf, W.H. (1967). Transport in the central nervous system. Proc. Roy. Soc. Med., 60, 326–328PubMedPubMedCentralGoogle Scholar
  48. Davson, H. and Segal, M.B. (1970). The effects of some inhibitors and accelerators of sodium transport on the turnover of 22Na in the cerebrospinal fluid. J. Physiol., 209, 131–153CrossRefPubMedPubMedCentralGoogle Scholar
  49. Davson, H., Welch, K. and Segal, M.B. (1987). Physiology and Pathophysiology of the Cerebrospinal Fluid. Churchill Livingstone, EdinburghGoogle Scholar
  50. Denbow, D.M. and Myers, R.D. (1982). Eating, drinking and temperature responses to intracerebroventricular cholecystokinin in the chick. Peptides, 3, 739–743CrossRefGoogle Scholar
  51. Derian, C.K. and Moskowitz, M.A. (1986). Polyphosphoinoside hydrolysis in endothelial cells and carotid artery segments. Bradykinin-2 receptor stimulation is calcium-dependent. J. Biol. Chem., 261, 3831–3837PubMedGoogle Scholar
  52. de Sousa, E.B. and Kuhar, H.J. (1986). Corticotrophin-releasing factor receptors: autoradiographic identification. In Martin, J.B. and Barchas, J.D. (Eds), Neuropeptides in Neurologic and Psychiatric Disease. Raven Press, New York, pp. 179–198Google Scholar
  53. de Wied, D. (1987). The neuropeptide concept. In de Kloet, E.R., Wiegant, N.M. and de Wied, D. (Eds), Neuropeptides and Brain Function. Progress in Brain Research, Vol. 72, Elsevier, Amsterdam, pp. 93–108CrossRefGoogle Scholar
  54. de Wied, D., Gaffori, O., van Ree, J.M. and de Jong, W. (1984). Central target for the behavioral effects of vasopressin peptides. Nature, 308, 276–278CrossRefGoogle Scholar
  55. Dickson, P.W., Aldred, A.P., Marley, P.D., Guo-Fen, T., Howlett, G J. and Schreiber, G. (1985). High prealbumin and transferrin mRNA levels in the choroid plexus of rat brain. Biochem. Biophys. Res. Commun., 127, 890–895CrossRefPubMedGoogle Scholar
  56. Doczi, T., Joó, F., Szerdahelyi, P. and Bodosi, M. (1988). Regulation of brain water and electrolyte contents: the opposite actions of central vasopressin and atrial natriuretic factor (ANF). Acta Neurochir., 43, (Suppl.), 186–188Google Scholar
  57. Dodd, J. and Kelly, J.S. (1981). The actions of cholecystokinin and related peptides on pyramidal neurones of the mammalian hippocampus. Brain Res., 205, 337–356CrossRefPubMedGoogle Scholar
  58. Du Vigneaud, V. (1954). Hormones of the posterior pituitary gland: oxytocin and vasopressin. Harvey Lectures, 50, 1–26Google Scholar
  59. Dux, E. and Joó, F. (1982). Effects of histamine on brain capillaries: fine structural and immunohistochemical studies after intracarotid infusion. Exp. Brain Res., 47, 252–258CrossRefPubMedGoogle Scholar
  60. Dziegielewska, K.M. and Saunders, N.R. (1988a). The development of the blood-brain barrier: proteins in fetal and neonatal CSF, their nature and origins. In Meisami, E. and Timiras, P.J. (Eds), Handbook of Human Growth and Biological Development. CRC Press, Boca Raton, Florida, pp. 103–118Google Scholar
  61. Dziegielewska, K.M. and Saunders, N.R. (1988b). The origins and functions of proteins in CSF in the developing brain. In Rakić, L., Begley, D.J., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 105–121Google Scholar
  62. Edvinsson, L., Fahrenburg, J., Hanko, J., McCulloch, J., Owman, C. and Uddman, R. (1981). Vasoactive intestinal polypeptide and effects on cerebral blood flow and metabolism. In Cervos-Navarro, J. and Fritschka, E. (Eds),Cerebral Blood Flow and Metabolism. Raven Press, New York, pp. 147–155Google Scholar
  63. Ermisch, A. (1987). Blood-brain barrier and peptides. Wiss. Z. Karl-Marx-Univ. Leipzig, Math.-Naturmiss. R., 36, 72–77Google Scholar
  64. Ermisch, A., Landgraf, R., Brust, P., Kretzschmar, R. and Hess, J. (1988). Peptide receptors of the cerebral capillary endothelium and the transport of amino acids across the blood–brain barrier. In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 43–55Google Scholar
  65. Ermisch, A., Landgraf, R. and Mobius, P. (1986). Vasopressin and oxytocin in brain areas of rats with high or low behavioral performance. Brain Res., 379, 21–29CrossRefGoogle Scholar
  66. Fahzenkrug, J. (1979). Vasoactive intestinal polypeptide: measurement distribution and putative neurotransmitter function. Digestion, 19, 149–169CrossRefGoogle Scholar
  67. Feldman, S.C. and Kastin, A.J. (1984). Localization of neurones containing immunoreac-tive delta sleep-inducing peptide in the rat brain: an immunocytochemical study. Neuroscience, 11, 303–317CrossRefGoogle Scholar
  68. Figlewicz, D.P., Lacour, F., Sipols, A., Porte, Jr., D. and Woods, S.C. (1987). Gastroenter-opancreatic (GEP) peptides in the central nervous system. Ann. Rev. Physiol., 49, 383–395CrossRefGoogle Scholar
  69. Frank, H.J.L., Jankovic-Vokis, T., Pardridge, W.M. and Morris, W.L. (1985). Enhanced insulin binding to blood-brain barrier in vivo and to brain microvessels in vitro in newborn rabbits. Diabetes, 34, 728–733CrossRefGoogle Scholar
  70. Frank, H.J.L., Pardridge, W.M., Morris, W.L., Rosenfeld, R.G. and Choi, T.B. (1986). Binding and internalization of insulin and insulin-like growth factors by isolated brain microvessels. Diabetes, 35, 654CrossRefGoogle Scholar
  71. Freedman, F. and Johnson, J. (1969). Equilibrium and kinetic properties of the Evans blue-albumin system. Am. J. Physiol., 216, 675–681PubMedGoogle Scholar
  72. Gafford, J.T., Skidgel, R.A., Erdos, E.G. and Hersh, L.B. (1983). Human kidney ‘enkephalinase’, a neutral metalloendopeptidase that cleaves active peptides. Biochemistry, 22, 3265–3271CrossRefGoogle Scholar
  73. Gaudreau, P., Quirion, R., St. Pierre, S. and Pert, C.B.(1983). Characterization and visualization of cholecystokinin receptors in rat brain using 3H-pentagastrin. Peptides, 4, 755–762CrossRefGoogle Scholar
  74. Giles, T.D. and Sander, G.E. (1983). Mechanism of the cardiovascular response to systemic intravenous administration of leucine-enkephalin in the conscious dog. Peptides, 4, 171–175CrossRefGoogle Scholar
  75. Gjedde, A. (1988). Exchange diffusion of large neutral amino acids between blood and brain. In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V.(Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 213–223Google Scholar
  76. Gjedde, A. and Bodsch, W. (1987). Facilitated diffusion across the blood-brain barriers interactions between receptors and transporters. Wiss. Z. Karl-Marx Univ. Leipzig, Math.-Naturmiss. R., 36 (1), 67–71Google Scholar
  77. Gold, P.W. and Chrousos, G.P. (1985). Clinical studies with corticotropin releasing factor: implications for diagnosis and pathophysiology of depression, Cushing’s disease, and adrenal insufficiency. Psychoneuroendocrinology, 10, 401–419CrossRefGoogle Scholar
  78. Gold, P.W., Chrousos, G., Kellner, C., Post, R., Roy, A., Augerinos, P., Schulte, H., Oldfield, E. and Loriaux, D.L. (1984). Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am. J. Psychiat., J41, 619–623Google Scholar
  79. Goldman, H. and Murphy, S. (1981). An analog of ACTH/MSH ORG-2766, reduces permeability of the blood-brain barrier. Pharmacol. Biochem. Behav., 14, 845–848CrossRefPubMedGoogle Scholar
  80. Goldmann, E.E. (1909). Die äussere und innere secretetion des gesunden und kranken organismus im lichte der ‘vitalon tarbung’. Beitz. Klin. Chiurg., 64, 192–265Google Scholar
  81. Goldmann, E.E. (1913). Vitalfarbung am Zentral Nervensystem (Abh. Preuss. Akad. Wiss.). Phys Math. Kl., 1, 1–60Google Scholar
  82. Goodman, R.F., Fricker, L.D. and Snyder, S.H. (1983). Enkephalins. In Kreiger, D.T., Browstein, J. and Martin, J.B. (Eds), Brain Peptides. Wiley, New York, pp. 828–849Google Scholar
  83. Greig, N.H. (1989). Drug delivery to the brain by blood-brain barrier circumvention and drug modification. In Neuwelt, E.A. (Ed.), Implications of the Blood-Brain Barrier and Its Manipulation. Plenum Medical Book Company, New York, pp. 311–312CrossRefGoogle Scholar
  84. Griffin, D.E. and Giffels, J. (1982). Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis. J. Clin. Invest., 70, 289–293CrossRefPubMedPubMedCentralGoogle Scholar
  85. Gros, C., Giros, B. and Schwartz, J.C. (1985). Identification of aminopeptidase M as an enkephalin-inactivating enzyme in rat cerebral membranes. Biochemistry, 24, 2179–2185CrossRefGoogle Scholar
  86. Gross, P.M., Kadekaro, M., Andrews, D.W., Sokoloff, L. and Saavedra, J.M. (1985). Selective metabolic stimulation of the subfornical organ and pituitary neural lobe by peripheral angiotensin II. Peptides, 6 (Suppl. 1), 145–152CrossRefGoogle Scholar
  87. Guglietta, A., Strunk, C.L., Irons, B.J. and Lazarus, L.H. (1985). Central neuromodulation of gastric acid secretion by bombesin-like peptides. Peptides, 6 (Suppl. 3), 75–81CrossRefGoogle Scholar
  88. Hanko, J., Hardebo, J.E. and Owman, C. (1981). In Cervos-Navarro, J. and Fritschka, E. (Eds), Cerebral Microcirculation and Metabolism. Raven Press, New York, pp. 157–161Google Scholar
  89. Harbaugh, R.E., Roberts, D.W., Coombs, D.W., Saunders, R.L. and Reeder, T.M. (1984). Preliminary report: intracranial cholinergic drug infusion in patients with Alzheimer’s disease. Neurosurgery, 15, 514–517CrossRefGoogle Scholar
  90. Hassen, A.H., Feuerstein, G. and Faden, A.I. (1983). Differential cardiovascular effects mediated by mu and kappa opiate receptors in hindbrain nuclei. Peptides, 4, 621–625CrossRefGoogle Scholar
  91. Heidenreich, K.A., Zahniser, N.R., Berhanu, P., Brandenburg, D. and Olefsky, J.M. (1983). Structural differences between insulin receptors in the brain and peripheral target tissues. J. Biol. Chem., 258, 8527–8530PubMedGoogle Scholar
  92. Hersch, L.B. (1982). Degradation of enkephalins: the search for an enkephalinase. Mol. Cell Biochem., 47, 35–43Google Scholar
  93. Hersch, L.B., Aboukhair, N. and Watson, S. (1987). Immunohistochemical localization of aminopeptidase M in rat brain and periphery: relationship of enzyme localization and enkephalin metabolism. Peptides, 8, 523–532CrossRefGoogle Scholar
  94. Hess, J., Gjedde, A. and Jessen, H. (1987). Vasopressin receptors at the blood-brain barrier in rats. Wiss. Z. Karl-Marx-Univ. Leipzig, Math.-Naturmiss. R., 36, 81–83Google Scholar
  95. Hoehler, F.K. and Sandman, C.A.(1981). Effects of alpha-MSH and beta-endorphin on startle reflex in rat. Peptides, 2, Suppl. 1, 137–141CrossRefGoogle Scholar
  96. Hoffman, P.L., Szabo, G. and Tabakoff, B. (1988). The effects of vasopressin and related peptides on tolerance to ethanol. In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 147–156CrossRefGoogle Scholar
  97. Hoffman, P.L., Walter, R. and Bulat, M. (1977). An enzymatically stable peptide with activity in the central nervous system: its penetration through the blood-CSF barrier. Brain Res., 122, 87CrossRefPubMedGoogle Scholar
  98. Holtman, J.R., Buller, A.L., Hamosh, P. and Gillis, R. (1986). Central respiratory stimulation produced by thyrotropin-releasing hormone in the cat. Peptides, 7, 207–212CrossRefGoogle Scholar
  99. Hoosein, N.M. and Gurd, R.S. (1984). Identification of glucagon receptors in rat brain. Proc. Natl Acad. Sci. USA, 84, 4368–4372CrossRefGoogle Scholar
  100. Huang, J.T. (1982). Accumulation of peptides by choroid plexus in vitro: Tyr-D-Ala-Gly as a model. Neurochem. Res., 7, 1541–1548CrossRefGoogle Scholar
  101. Huang, J.T. and Lajtha, A. (1978). The accumulations of 3H-enkephalinamide (2-D-alanine-5-methioninamide) in rat brain tissues. Neuropharmacology, 17, 1075–1079CrossRefGoogle Scholar
  102. Huang, M., Hanley, D.A. and Rorstad, O.P. (1983). Parathyroid hormone stimulates adenylate cyclase in rat cerebral microvessels. Life Sci., 32, 1009–1014CrossRefPubMedGoogle Scholar
  103. Huang, M. and Rorstad, O.P. (1983). Effects of vasoactive intestinal polypeptide, monoamines, prostaglandins and 2-choloroadenosine on adenylate cyclase in rat cerebral microvessels. J. Neurochem., 40, 719–726CrossRefPubMedGoogle Scholar
  104. Huffman, L.J., Campbell, G.T. and Gilmore, J.P. (1983). Renal function and pituitary hormone release during cerebral osmostimulation and TRH in dogs. Peptides, 4, 843–847CrossRefGoogle Scholar
  105. Hughes, J., Smith, T.W., Kosterlitz, H.W., Fothergill, L.A., Morgan, B.A. and Morris, H.R. (1975). Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature, 258, 577–579CrossRefGoogle Scholar
  106. Hurley, J.V., Anderson, R.McD. and Sexton P.T. (1981). The fate of plasma protein which escapes from blood vessels of the choroid plexus of the rat-An electron microscopic study. J. Pathol., 134, 57–70CrossRefPubMedGoogle Scholar
  107. Iversen, L.L., Lee, C.M., Gilbert, R.F., Hunt, S. and Emson, P.C. (1980). Regulation of neuropeptide release. Proc. R. Soc., 210, 91–111CrossRefGoogle Scholar
  108. Jackson, I.M. and Lechan, R.M. (1983). Thyrotropin releasing hormone. In Kreiger, D.T., Browstein, J. and Martin, J.B. (Eds), Brain Peptides. Wiley, New YorkGoogle Scholar
  109. Jeffries, W.A., Brandon, M.R., Hunt, S.V., Williams, A.F., Gatter, K.C. and Mason, D.Y. (1984). Transferrin receptor on endothelium of brain capillaries. Nature, 312, 162CrossRefGoogle Scholar
  110. Johanson, C.E. (1989). Potential for pharmacological manipulation of the blood-cerebrospinal fluid barrier. In Neuwelt, E.A. (Ed.), Implications of the Blood-Brain Barrier and Its Manipulation. Plenum Medical Book Company, New York, pp. 223–261CrossRefGoogle Scholar
  111. Jones, P.M. and Robinson, I.C.A.F. (1982). Clearance of neurohypophysial peptides from cerebrospinal fluid. J. Physiol., 326, 23PGoogle Scholar
  112. Joó, F. (1972). Effect of N6, O6-dibutyryl cyclic 3’,5’-adenosine monophosphate on the pinocytosis of brain capillaries in mice. Experientia, 28, 1470–1471CrossRefGoogle Scholar
  113. Joó, F. (1986). New aspects to the function of the cerebral endothelium. Nature, 321, 197–198CrossRefGoogle Scholar
  114. Joó, F. (1988). Cyclic nucleotide-mediated regulation of albumin transport in brain microvessels. In Rakić, Lj., Begley, DJ., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 119–128CrossRefGoogle Scholar
  115. Joó, F., Temesvari, P. and Dux, E. (1983). Regulation of the macromolecular transport in the brain microvessels: the role of cyclic GMP. Brain Res., 278, 165–174 CrossRefPubMedGoogle Scholar
  116. Kabat, E.A., Moore, D.H. and Landow, H. (1942). An electrophoretic study of the protein components in the cerebrospinal fluid and their relationship to serum protein. J. Clin. Invest., 21, 571–577CrossRefPubMedPubMedCentralGoogle Scholar
  117. Kalin, N.H., Shelton, S.E., Kraemer, G.W. and McKinney, W.T. (1983). Associated endocrine, physiological and behavioral changes in Rhesus monkeys after intravenous corticotropin-releasing factor administration. Peptides, 4, 211–215CrossRefGoogle Scholar
  118. Kapadia, S.E. and DeLanerolle, N.C. (1984). Immunohistochemical and electron micro-scopic demonstration of vascular innervation in the mammalian brainstem. Brain Res., 292, 33–39CrossRefPubMedGoogle Scholar
  119. Karnushina, I., Palacios, J.M., Barbin, G., Dux, E., Joó, F. and Schwartz, J.C. (1980). Studies on a capillary-rich fraction isolated from brain: histaminic components and characterization of the histamine receptors linked to adenylate cyclase. J. Neurochem., 34, 1201–1208CrossRefPubMedGoogle Scholar
  120. Kastin, A.J. and Dickson, J.C. (1987). Hypophysectomy increases Tyr-MIF-1 like immunoreactivity in rat plasma. Neuroendocrinology, 45, 177–181CrossRefGoogle Scholar
  121. Kastin, A.J., Nissan, C. and Coy, D.H. (1981). Permeability of blood-brain barrier to DSIP peptides. Pharmacol. Biochem. Behav., 15, 955–959CrossRefPubMedGoogle Scholar
  122. Kastin, A.J., Nissan, C., Schally, A.V. and Coy, D.H. (1976). Blood-brain barrier, half time disappearance, and brain distribution for labeled enkephalin and a potent analog. Brain Res. Bull., 1, 583–589CrossRefPubMedGoogle Scholar
  123. Kastin, A.J., Olson, R.D., Schally, A.V. and Coy, D.H. (1979). CNS effects of peripherally administered peptides. Life Sci., 25, 401–414CrossRefPubMedGoogle Scholar
  124. Katusic, Z.S., Shepherd, J.T. and Vanhoutte, P.M. (1984). Vasopressin causes endothe-lium-dependent relaxations of the canine basilar artery. Circ. Res., 55 (5), 575–579CrossRefPubMedGoogle Scholar
  125. Katusic, Z.S., Shepherd, J.T. and Vanhoutte, P.M. (1986). Oxytocin causes endothelium-dependent relaxations of canine basilar arteries by activating Vl-vasopressinergic recep-tors. J. Pharmacol. Exp. Ther., 236, 166–170PubMedGoogle Scholar
  126. Kordon, C., Blauet-Pajot, M.T., Clausen, H., Drouva, S., Enjabert, A. and Epelbaum, Y. (1987). New designs in neuroendocrine systems. In de Kloet, E.R., Wiegant, N.M. and de Wied, D.C. (Eds), Neuropeptides and Brain Function. Progress in Brain Research, Vol. 72, Elsevier, Amsterdam, pp. 27–34CrossRefGoogle Scholar
  127. Koslo, R.J., Gmerek, D.E. and Porreca, F. (1986). Intrathecal bombesin-induced inhibition of gastrointestinal transit: requirement for an intact pituitary-adrenal axis. Reg. Peptides, 14, 237–242CrossRefGoogle Scholar
  128. Kowarski, D., Shuman, H., Somlyo, A.P. and Somlyo, A.V. (1985). Calcium release by noradrenaline from central sarcoplasmic reticulum in rabbit main pulmonary artery smooth muscle. J. Physiol., 366, 153–175CrossRefPubMedPubMedCentralGoogle Scholar
  129. Kragh-Hansen, U. (1981). Molecular aspects of ligand binding to serum albumin. Pharmacol. Rev., 33, 17–53PubMedGoogle Scholar
  130. Kretzschmar, R., Landgraf, R., Gjedde, A. and Ermisch, A. (1986). Vasopressin binds to microvessels from rat hippocampus. Brain Res., 380, 325–330CrossRefPubMedGoogle Scholar
  131. Kreiger, D.T. (1986). An overview of neuropeptides. In Martin, J.B. and Barchas, J.D. (Eds), Neuropeptides in Neurologic and Psychiatric Diseases. Raven Press, New York, pp. 1–32Google Scholar
  132. Kumagai, A.K., Eisenberg, J. and Pardridge, W.M. (1986). Rapid binding and internaliza-tion of cationized albumin by isolated brain capillaries. Clin. Res., 34, 69AGoogle Scholar
  133. Kumagai, A.K., Eisenberg, J. and Pardridge, W.M. (1987). Absorption-mediated endocy-tosis and cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport. J. Biol. Chem.,262,15214–15219PubMedGoogle Scholar
  134. Lackoff, A. and Jackson, I.M.D. (1981). Calcium dependency of potassium-stimulated thyrotropin-releasing hormone secretion from rat neurohypophysis in vitro. Neurosci. Lett., 27, 17Google Scholar
  135. Landgraf, R., Hess, J. and Ermisch, A. (1978). The influence of vasopressin on the regional uptake of [3H]orotic acid by rat brain. Acta Biol. Med. Ger., 37, 655–658PubMedGoogle Scholar
  136. Landgraf, R., Hess, J. and Hartmann, E. (1977). Der Einfluss von Ocytocin auf die regionale 3H Orotsaure-Aufnahme durch das Rattengehirn. Endokrinologie, 70, 45–52Google Scholar
  137. Lee, R.J. and Lomax, P. (1983). Thermoregulatory, behavioral and seizure modulatory effects of AVP in the gerbil. Peptides, 4, 801–805CrossRefGoogle Scholar
  138. Lenhard, L. and Deftos, L.J. (1982). Adenohypophysial hormones in the CSF. Neuro-endocrinology, 34, 303–308CrossRefGoogle Scholar
  139. Levin, MJ., Tuil, D., Uzan, G., Dreyfus, J.C. and Kahn, A. (1984). Expression of the transferrin gene during development of nonhepatic tissues: high levels of transferrin mRNA in fetal muscle and adult brain. Biochem. Biophys. Res. Commun., 122, 212CrossRefPubMedGoogle Scholar
  140. Levine, R., Frederics, W. and Rapoport, S. (1982). Entry of bilirubin into the brain due to opening of the blood-brain barrier. Pediatrics, 69, 255–259Google Scholar
  141. Levitan, H., Ziylan, Z., Smith, Q. et al. (1984). Brain uptake of food dye, erythrosin B, prevented by plasma protein binding. Brain Res., 322, 131–134CrossRefPubMedGoogle Scholar
  142. Lipton, J.M. and Glyn, J.R. (1980). Central administration of peptides alters thermoregula-tion in the rabbit. Peptides, 1, 15–18CrossRefGoogle Scholar
  143. McComb, J.G. (1983). Recent research into the nature of cerebrospinal fluid formation and absorption. J. Neurosurg, 59, 369–383CrossRefGoogle Scholar
  144. McKinley, M.J., Allen, A., Clevers, T., Dentin, D.A., Mendlesohn, F.A.O., Oldfield, B.J., Tarjan, E. and Weisirger, R.S. (1987). Angiotensin II receptors in the brain of the sheep. Wiss. Z. Karl-Marx-Univ. LeipzigMath.-Naturwiss. R., 36, 189–192Google Scholar
  145. Makara, G.B. (1985). Mechanism by which stressful stimuli activate the pituitary-adrenal system. Fed. Proc., 45, 149–153Google Scholar
  146. Matsas, R., Stephenson, S.L., Hryszko, J., Kenny, A.J., and Turner, A.J. (1985). The metabolism of neuropeptides: phase separation of synaptic membrane preparations with triton X-114 reveals the presence of aminopeptidase N. Biochem. J., 231, 445–449CrossRefPubMedGoogle Scholar
  147. Matsumoto, T., Kanaide, H., Nishimura, J., Shogakiuchi, Kobayshi, S. and Nakamura, M. (1986). Histamine activates H1-receptors to induce cytosolic free calcium transients in cultured vascular smooth muscle cells from rat aorta. Biochem. Biophys. Res. Commun., 135, 172–177CrossRefPubMedGoogle Scholar
  148. Meisenberg, G. and Simmons, W.H. (1983). Peptides and the blood-brain barrier. Life Sci., 32, 2611–2633CrossRefPubMedGoogle Scholar
  149. Mess, B. and Trentini, G.P. (1974). 3H-melatonin level in cerebrospinal fluid and choroid plexus following intravenous administration of the labeled compound. Acta Physiol. Acad. Sci. Hung., 45, 225–231PubMedGoogle Scholar
  150. Milhorat, T.H., Davis, D.A. and Lloyd, B.J. (1973). Two morphologically distinct blood-brain barriers preventing entry of cytochrome c into cerebrospinal fluid. Science, 180, 76–78CrossRefGoogle Scholar
  151. Møllgard, K., Balslev, Y. and Saunders, N. (1988). Structural aspects of the blood-brain and blood-CSF barriers with respect to endogenous proteins. In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V. (Eds). Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 93–101CrossRefGoogle Scholar
  152. Møllgard, K. and Saunders, N.R. (1977). A possible transepithelial pathway via endoplas-mic reticulum in foetal sheep choroid plexus. Proc. Roy. Soc. B, 199, 321–326CrossRefGoogle Scholar
  153. Møllgard, K. and Saunders, N.R. (1986). The development of the human blood-brain and blood-CSF barriers. Neuropath. Appl. Neurobiol., 12, 337–358CrossRefGoogle Scholar
  154. Moody, T.W., O’Donohue, T.L. and Jacobowitz, D.M. (1981). Biochemical localization and characterization of bombesin-like peptides in discrete regions of rat brain. Peptides, 2, 75–79CrossRefGoogle Scholar
  155. Morimoto, S., Nishimura, J., Miyauchi, A., Takai, S.I., Okada, Y., Onishi, T., Fukuo, K., Lee, S. and Kumahara, Y. (1982). Calcitonin in plasma and cerebrospinal fluid from normal subjects and patients with medullary thyroid carinoma: possible restriction of calcitonin by blood-brain barrier. J. Clin. Endocrinol. Metab., 55, 597–596CrossRefGoogle Scholar
  156. Morley, J.E., Levine, A., Oken, M.M., Grace, M. and Kneip, J. (1982). Neuropeptides and thermoregulation: the interactions of bombesin, neurotensin, TRH, somatostatin, nalox-one and prostaglandins. Peptides, 3, 1–6CrossRefGoogle Scholar
  157. Neuwelt, E.A. and Rapoport, S.I. (1984). Modification of the blood-brain barrier in the chemotherapy of malignant brain tumors. Fed. Proc., 43, 214–221PubMedGoogle Scholar
  158. Niewoehner, D.E., Levine, A.S. and Morley, J.E. (1983). Central effects of neuropeptides on ventilation in the rat. Peptides, 4, 277–281CrossRefGoogle Scholar
  159. North, A.R. (1986). Electrophysiological effects of neuropeptides. In Martin, J.B. and Broebes, J.D. (Eds), Neuropeptides in Neurologic and Psychiatric Disease. Raven Press, New York, pp. 71–77Google Scholar
  160. Ohno, K., Pettigrew, K.D. and Rapoport, S.I. (1978). Lower limits of cerebrovascular permeability to non-electrolytes in conscious rat. Am. J. Physiol., 235, H299–H307Google Scholar
  161. Oldendorf, W.M. (1981). Blood-brain barrier permeability to peptides, pitfalls in measure-ment. Peptides, 2 (Suppl. 2), 109–111CrossRefGoogle Scholar
  162. Ommaya, A. (1963). A subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet ii, 983–984CrossRefGoogle Scholar
  163. Pardridge, W.M. (1979). Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: Primary role of albumin-bound hormone. Endocrinol., 105, 605–612CrossRefGoogle Scholar
  164. Pardridge, W.M. (1981). Transport of protein-bound hormones into tissues in vivo. Endocrin. Rev., 2, 103–123CrossRefGoogle Scholar
  165. Pardridge, W.M. (1985). Strategies for drug delivery through the blood-brain barrier. In Borchardt, R.T., Repta, A.J. and Stella, V.J. (Eds), Directed Drug Delivery: A Multidisci-plinary Problem. Humana Press Inc., Clifton, N.J. p. 83CrossRefGoogle Scholar
  166. Pardridge, W.M. (1986a). Receptor-mediated peptide transport through the blood-brain barrier. Endocr. Rev., 7 (3), 31–33Google Scholar
  167. Pardridge, W.M. (1986b). Blood-brain barrier: interface between internal medicine and the brain. Ann. Intern. Med., 105, 82–95CrossRefPubMedGoogle Scholar
  168. Pardridge, W.M. (1987). Plasma protein mediated transport of steroid and thyroid hormones. Am. J. Physiol., 252, E157–E164Google Scholar
  169. Pardridge, W.M. (1988). Recent advances in blood-brain barrier transport. Ann. Rev. Pharmacol. Toxicol., 28, 25–39CrossRefGoogle Scholar
  170. Pardridge, W.M., Eisenberg, J. and Cefalu, W.T. (1985a). Absence of albumin receptor on brain capillaries in vivo or in vitro. Am. J. Physiol., 249, E264Google Scholar
  171. Pardridge, W.M., Eisenberg, J. and Yang, J. (1985b). Human blood-brain barrier insulin receptor. J. Neurochem., 44, 1771CrossRefPubMedGoogle Scholar
  172. Pardridge, W.M., Eisenberg, J. and Yang, J. (1987). Human blood-brain barrier transferrin receptor. J. Neurochem., 49, 1394–1401CrossRefPubMedGoogle Scholar
  173. Pardridge, W.M. and Oldendorf, W.H. (1975). Kinetic analysis of blood-brain barrier transport of amino acids. Biochim. Biophys. Acta, 401, 128–136CrossRefGoogle Scholar
  174. Pardridge, W.M., Triguero, D. and Buciak, J.L. (1990). β-Endorphin chimeric peptides: transport through the blood-brain barrier in vivo and cleavage of disulfide linkage by brain. Endocrinology, 126 (2), 977–984CrossRefGoogle Scholar
  175. Patel, H.M. (1984). Liposomes: bags of challenge. Biochem. Soc. Trans., 12, 333CrossRefPubMedGoogle Scholar
  176. Peterson, J.S., Kalivas, P.W. and Prasad, C. (1984). Cyclo (His-Pro) (cHP) regulates striatal dopaminergic function. Soc. Neurosci. Abstr., 10, 1123Google Scholar
  177. Posner, B.I., van Houten, M., Patel, B. and Walsh, R.J. (1983). Characterization of lactogen binding sites in choroid plexus. Exp. Brain, 49, 300–306CrossRefGoogle Scholar
  178. Prange, A.J., Gazzbutt, J., Loosen, P.T., Bissette, G. and Nemeroff, C.B. (1987). The role of peptides in affective disorders: a review. Prog. Brain Res., 72, 235–279CrossRefPubMedGoogle Scholar
  179. Prange Jr, AJ., Wilson, I.C., Lara, P.P., Alltop, L.B. and Breese, G.R. (1972). Effects of thyroptropin releasing hormone in depression. Lancet, ii, 999–1002CrossRefGoogle Scholar
  180. Rap, Z.M. (1981). Inhibitory effect of antidiuretic hormone on outflow of the cerebrospinal fluid in vasogenic brain edema induced by cold lesion. In Cervos-Navarro, J. and Fritschke, E. (Eds), Cerebral Microcirculation and Metabolism. Raven Press, New York, pp. 171–175Google Scholar
  181. Rap, Z.M., Kozniewska, E. and Skolasinska, K. (1980). Effect of vasopressin on cerebral blood flow and cerebrospinal fluid outflow. In Betz, E., Grobe, J. and Hauser, D. (Eds), Pathophysiology and Pharmacotherapy of Cerebrovascular Disorders. Verlag G. Witzstrock, Köln, pp. 12–14Google Scholar
  182. Rapoport, S.I., Klee, W.A., Pettigrew, K.D. and Olmo, K. (1980). Entry of opioid peptides into the central nervous system. Science, 207, 84–86CrossRefGoogle Scholar
  183. Reese, T.S., Feder, N. and Brightman, M.W. (1971). Electron microscopic study of the blood-brain and blood-cerebrospinal fluid barriers with microperoxidase. J. Cell. Biol, 34, 207–217CrossRefGoogle Scholar
  184. Reese, T.S. and Karnovsky, M.J. (1967). Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol., 34, 207–217CrossRefPubMedPubMedCentralGoogle Scholar
  185. Reichlin, S. (1983a). Somatostatin. New Engl. J. Med., 309, 1495–1501CrossRefPubMedGoogle Scholar
  186. Reichlin, S. (1983b). Somatostatin. New Engl. J. Med., 309, 1556–1562CrossRefPubMedGoogle Scholar
  187. Reith, J., Ermisch, A., Diemer, N.H. and Gjedde, A. (1987). Saturable retention of vasopressin by hippocampus vessels in vivo, associated with inhibition of blood-brain transfer of large neutral amino acids. J. Neurochem., 49, 1471–1479CrossRefPubMedGoogle Scholar
  188. Rivier, C. and Vale, W. (1985). Effects of corticotropin-releasing factor, neurohypophyseal peptides and catecholamines on pituitary function. Fed. Proc., 44, 189–195PubMedGoogle Scholar
  189. Rogers, R.C. and Hermann, G.E. (1985). Dorsal medullary oxytocin, vasopressin, oxytocin antagonist, and TRH effects on gastric acid secretion and heart rate. Peptides, 6, 1143–1148CrossRefGoogle Scholar
  190. Sandman, C.A., Beckwith, B.E. and Kastin, A.J. (1980). Are learning and attention related to the sequence of amino acids in ACTH/MSH peptides? Peptides, 1, 277–280CrossRefGoogle Scholar
  191. Sarna, G.S., Bradbury, M.W.B. and Cavanagh, J. (1978). Permeability of the blood-brain barrier after porto-caval anastomosis in the rat. Brain Res., 138, 550–554CrossRefGoogle Scholar
  192. Schaffer, M.M. and Moody, T.W. (1986). Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide. Peptides, 7, 283–286CrossRefGoogle Scholar
  193. Schivers, B.D., Harlan, R.E., Romano, J.G., Howills, R.D. and Phaff, G.W. (1986). Cellular localization of pre-enkephalin in RNA in rat brain: gene expression in the caudate putamen and cerebral cortex. Proc. Natl Acad. Sci. USA, 83, 6221–6225CrossRefGoogle Scholar
  194. Schutz, W., Steuer, G. and Tuisl, E. (1982). Functional identification of adenylate cyclase-coupled adenosine receptors in rat brain microvessels. Eur. PharmacoL, 85, 177–184CrossRefGoogle Scholar
  195. Schwartz, J.C. (1983). Metabolism of enkephalins and the inactivating peptide concept. Trends Neursci., 6, 5–8CrossRefGoogle Scholar
  196. Schwartz, J.C., Malfroy, B. and De La Baume, S. (1981). Biological inactivation of enkephalins and the role of enkephalin dipeptidyl-carboxypeptidase (‘Enkephalinase’) as neuropeptidase. Life Sci., 29, 1715–1740CrossRefPubMedGoogle Scholar
  197. Segal, M.B. and Pollay, M. (1977). The secretion of cerebrospinal fluid. Exp. Eye Res., 25 (Suppl.), 205–228Google Scholar
  198. Segal, M.B. and Zloković, B.V. (1990). The Blood-Brain Barrier, Amino Acids and Peptides, Kluwer, Dordrecht, Boston, LondonGoogle Scholar
  199. Siggins, G.R. and Groul, D.L. (1986). Synaptic mechanisms in the vertebrate central nervous system. In Bloom, F.E. (Ed.), Handbook of Physiology. Volume on Intrinsic Regulatory Systems of the Brain. American Physiological Society, Bethesda, Maryland, pp. 1–114Google Scholar
  200. Simantov, R. and Snyder, S.H. (1976). Morphine-like peptides in mammalian brain: isolation, structure, elucidation, and interactions with opiate receptors. Proc. Natl Acad. Sci. USA, 73 (7), 2515–2519CrossRefGoogle Scholar
  201. Smith, Q.R., Momma, S., Aoyagi, M. and Rapoport, S.I. (1987). Kinetics of neutral amino acid transport across the blood-brain barrier. J. Neurochem., 49, 1651–1658Google Scholar
  202. Smith, Q.R., Takasato, Y. and Rapoport, S. (1984). Kinetic analysis of L-leucine transport across the blood-brain barrier. Brain Res., 311, 167–170CrossRefPubMedGoogle Scholar
  203. Spector, R. (1977). Vitamin homeostasis in the central nervous system. New Engl. J. Med., 296, 1393–1398CrossRefPubMedGoogle Scholar
  204. Spector, R. (1982). Nucleoside transport in choroid plexus: Mechanism and specificity. Arch. Biochem. Biophys., 216, 693–703CrossRefPubMedGoogle Scholar
  205. Speth, R.C. and Harik, S.I. (1985). Angiotensin II receptor binding sites in brain microvessels. Proc. Natl Acad. Sci USA, 82, 6340–6343CrossRefGoogle Scholar
  206. Strikant, C.B. and Patel, Y.C. (1981). Somatostatin receptors: identification and character-ization in rat brain membranes. Proc. Natl Acad. Sci. USA, 78, 3930–3934CrossRefGoogle Scholar
  207. Stephenson, S.L. and Kenny, A.J. (1987). The hydrolysis of alpha-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase 24.11. Biochem. J., 243, 183–187CrossRefPubMedPubMedCentralGoogle Scholar
  208. Stewart, P.A. and Wiley, M.J. (1981). Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail-chick transplantation chimeras. Dev. Biol, 84, 183–192CrossRefGoogle Scholar
  209. Stickrod, G., Kimble, D.P. and Smotherman, W.P. (1982). Met-enkephalin effects on associations formed in utero.Peptides, 3, 881–883CrossRefGoogle Scholar
  210. Susic, V. and Masirevic, G. (1988). In Rakić, Lj., Begley, D.J., Davson, H. and Zloković, B.V. (Eds), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System. Macmillan, London, pp. 141–147CrossRefGoogle Scholar
  211. Susic, V., Masirevic, G. and Totic, S. (1987). The effects of delta sleep inducing peptides (DSIP) on wakefulness and sleep patterns in the cat. Brain Res., 414, 262–270CrossRefPubMedGoogle Scholar
  212. Tache, Y., Vale, W., Rivier, J. and Brown, M. (1981). Brain regulation of gastric acid secretion in rats by neurogastrointestinal peptides. Peptides, 2 (Suppl. 2), 51–55CrossRefGoogle Scholar
  213. Takasato, J., Momma, S. and Smith, QR. (1985). Kinetic analysis of cerebrovascular isoleucine transport from saline and plasma. J. Neurochem., 45, 1013–1020CrossRefPubMedGoogle Scholar
  214. Takasato, Y., Rapoport, S.I. and Smith, QR. (1984). An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am. J. Physiol., 247, H484–H493Google Scholar
  215. Tenner, T.E.J., Yang, C.M., Chang, J.K., Schimizu, M. and Pang, P.K.T. (1980). Pharmacological comparison of bPTH-(1–34) and other hypotensive peptides in the dog. Peptides, 1, 285–288CrossRefGoogle Scholar
  216. Triguero, D.J., Buciak, J.B., Yang, J. and Pardridge, W.M. (1989). Blood-brain barrier transport of cationized inununoglobulin G: enhanced delivery compared to native protein. Proc. Natl Acad. Sci. USA, 86, 4761–4765CrossRefGoogle Scholar
  217. Uddman, R., Edvinsson, L., Owman, C. and Sundler, F. (1981). Perivascular substance P: occurrence and distribution in mammalian pial vessels. J. Cereb. Blood Flow Metab., 1, 227–232CrossRefPubMedGoogle Scholar
  218. Uddman, R., Edvinsson, L., Owman, C. and Sundler, F. (1983). Nerve fibres containing gastrin-releasing peptide around pial vessels. J. Cereb. Blood Flow Metab., 3, 386–390CrossRefPubMedGoogle Scholar
  219. Urban, I.J.A. (1981). Brain vasopressin: from electrophysiological effects to neurophysio-logical function. In de Kloet, E.R., Wiegant, V.M. and de Wied, D. (Eds), Neuropeptides and Brain Function. Progress in Brain Research, Vol. 72, pp. 163–172CrossRefGoogle Scholar
  220. Van der Velde, C.D. (1983). Rapid clinical effectiveness of MIF-1 in the treatment of major depressive illness. Peptides, 4, 297–300CrossRefGoogle Scholar
  221. van Deurs, B. (1977). Vesicular transport of horseradish peroxidase from brain to blood in segments of the cerebral microvasculature in adult mice. Brain Res., 124, 1–8CrossRefPubMedGoogle Scholar
  222. van Deurs, B. (1980). Structural aspects of brain barriers, with special reference to the permeability of the cerebral endothelium and choroidal epithelium. Intern. Rev. Cytol., 63, 117–191CrossRefGoogle Scholar
  223. van Deurs, B., von Bülow, F. and Meller, M. (1981). Vesicular transport of cationized ferritin by the epithelium of the rat choroid plexus. J. Cell Biol., 89, 131–139CrossRefPubMedGoogle Scholar
  224. Van Dijk, A., Richards, J.G., Trzeeiak, A., Gillessen, D. and Mohler, H. (1984). Cholecystokinin receptors: biochemical demonstration and autoradiographical localiza-tion in rat brain and pancreas using 3H-cholecystokinin as radioligand. J. Neurosci., 4, 1021–1033PubMedGoogle Scholar
  225. van Houten, M. and Posner, B.I. (1983). Circumventricular organs: receptors and mediators of direct peptide hormone action on brain. In Szabo, A. (Ed.), Advances in Metabolic Disorders, Vol. 10. Academic Press, New York, pp. 269–289Google Scholar
  226. Van Ree, J.M., Caffe, A.M. and Wolterink, G. (1982). Non-opiate beta-endorphin fragments and dopamine. III. γ-Type endorphins and various neuroleptics counteract the hypoactivity elicited by injection of apomorphine into the nucleus accumbens. Neuropharmacology, 21, 1111–1117CrossRefGoogle Scholar
  227. Van Ree, J.M., Verhoven, Z.K. and de Wied, D. (1987). Animal and clinical research on neuropeptides and schizophrenia. Prog. Brain Res., 72, 249–267CrossRefPubMedGoogle Scholar
  228. Varagic, V.M., Stojanovic, V. and Dzoljic, E. (1988). The effect of enkephalins and enkephalinase inhibitors on the central cholinergic mechanisms participating in the peripheral adrenergic activation. In Rakić, Lj., Begley, D.j., Davson, H. and Zloković, B.V. (Eds),Peptide and Amino Acid Transport Mechanisms in the Central Nervous System.Macmillan, London, pp. 157–166CrossRefGoogle Scholar
  229. Vistica, D.T. (1983). Cellular pharmacokinetics of the phenylalanine mustards. Pharmac. Ther., 22, 379–406CrossRefGoogle Scholar
  230. Walsh, R.J., Slaby, F. and Posner, B.I. (1987). Prolactin transport from blood to cerebrospinal fluid: a receptor mediated process. Wiss. Z. Karl-Marx-Univ. Leipzig Math.-Naturmiss. R., 36 (1), 119–120Google Scholar
  231. Wenger, T. (1987). The role of organum vasculosum of the lamina terminals in the regulation of pituitary gonadotrophic hormone secretion. Wiss. Z. Karl-Marx-Univ. Leipzig Math.-Naturroiss. R., 36 (1), 52–55Google Scholar
  232. Westergaard, E. and Brightman, M.W. (1973). Transport of proteins across normal cerebral arterioles. J. Comp. Neurol., 152, 17–44CrossRefPubMedGoogle Scholar
  233. Wilson, K.M. and Fregley, M.J. (1985). Factors affecting angiotensin II-induced hypother-mia in rats. Peptides, 6, 695–701CrossRefGoogle Scholar
  234. Winokur, A., Amsterdam, J., Caroff, S., Snyder, P.J. and Brunswich, D. (1982). Variability of hormonal responses to a series of neuroendocrine challenges in depressed patientsAm. J Psychiatr., 139, 39–44CrossRefPubMedGoogle Scholar
  235. Wolf, B.A., Turk, J., Sherman, W.R. and McDaniel, M.L. (1986). Intracellular Ca2+ mobilization by arachidonic acid. J. Biol. Chem., 261, 3501–3511PubMedGoogle Scholar
  236. Woods, S.C. and Porte, D. Jr. (1977). Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am. J. Physiol., 233, E331–E334Google Scholar
  237. Yarbrough, G.G. (1976). TRH potentiates excitatory actions of acetylcholine in cerebral cortical neurons. Nature, 263, 523–524CrossRefGoogle Scholar
  238. Zadina, J.E., Banks, W.A. and Kastin, J.E. (1986). Central nervous system effects of peptides 1980–1985. Peptides, 7, 497–537CrossRefGoogle Scholar
  239. Zerbe, R.L., Kirtland, S., Faden, A.I. and Feuerstein, G. (1983). Central cardiovascular effects of mammalian neurohypophysical peptides in conscious rats. Peptides, 4, 627–630CrossRefGoogle Scholar
  240. Zloković, B.V. (1990). In vivo approaches for studying peptide interactions at the blood-brain barrierJ.Control. Rel., 13, 185–202CrossRefGoogle Scholar
  241. Zloković, B.V., Begley, D.J. and Chain, D.G. (1983). Blood-brain barrier permeability to di-peptides and their constituent amino acids. Brain Res., 271, 66–71CrossRefGoogle Scholar
  242. Zloković, B.V., Begley, D.J. and Chain-Eliash, D.G. (1985a). Blood-brain barrier per-meability to leucine-enkephalin, D-alanine2 D-leucine5 -enkephalin and their N-terminal amino acid (tyrosine). Brain Res., 336 125–132CrossRefPubMedGoogle Scholar
  243. Zloković, B.V., Hyman, S., McComb, J.G., Tang, G., Davson, H. and Lipovać, M.N. (1990a). Kinetics of arginine-vasopressin uptake at the blood-brain barrier. Biochim. Biophys. Acta, 1025, 191–198CrossRefGoogle Scholar
  244. Zloković, B.V., Lipovac, N.M., Begley, D.J., Davson, H. and Rakić, Lj. (1987). Transport of leucine-enkephalin across the blood-brain barrier in the perfused guinea pig brain. J. Neurochem., 49, 310–315CrossRefPubMedGoogle Scholar
  245. Zloković, B.V., Lipovac, M.N., Begley, D.J., Davson, H. and Rakić, Lj. (1988a). Slow penetration of thyrotropin releasing hormone across the blood-brain barrier of in situ perfused guinea-pig brain. J. Neurochem., 51, 252–257CrossRefPubMedGoogle Scholar
  246. Zloković, B.V., McComb, J.G., Perlmutter, L. and Davson, H. (1991). Neuroactive Peptides and Amino Acids at the Blood-Brain Barrier: Possible Implications to Drug Abuse. NIDA Research Monographs, Washington, D.C. (in press)Google Scholar
  247. Zloković, B.V., Mackić, J.B., Duricić, B. and Davson, H. (1989a). Kinetic analysis of leucine-enkephalin cellular uptake by the blood-brain barrier of an in situ perfused guinea-pig brain. J. Neurochem., 53, 1333–1340CrossRefPubMedGoogle Scholar
  248. Zloković, B.V., Segal, M.B., Begley, D.J., Davson, D.J. and Rakić, Lj. (1985b). Permeabil-ity of the blood-cerebrospinal fluid and blood-brain barriers to thyrotropin releasing hormone. Brain Res., 358, 191–199CrossRefPubMedGoogle Scholar
  249. Zloković, B.V., Segal, M.B., Davson, H. and Jankov, R.M. (1988b). Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier. Peptides, 9, 533–538CrossRefGoogle Scholar
  250. Zloković, B.V., Skundrić, D., Segal, M.B., Lipovac, M.N., Mackić, J.B. and Davson, H. (1990b). A saturable mechanism for transport of immunoglobulin G across the blood-brain barrier of the guinea-pig. Exp. Neural., 107, 263–270CrossRefGoogle Scholar
  251. Zloković, B.V., Susić, V.T., Davson, H., Begley, D.J., Jankov, R.M., Mitrović, D.M. and Lipovac, M.N. (1989b). Saturable mechanisms for delta-sleep inducing peptide (DSIP) at the blood-brain barrier of the vascularly perfused guinea-pig brain. Peptides, 10, 249–254CrossRefGoogle Scholar

Copyright information

© The authors 1993

Authors and Affiliations

  • Hugh Davson
    • 1
  • Berislav Zloković
    • 2
  • Ljubisa Rakić
    • 3
  • Malcolm B. Segal
    • 1
  1. 1.Sherrington School of Physiology UMDSGuy’s and St Thomas’s HospitalsLondonUK
  2. 2.USC School of MedicineLos AngelesUSA
  3. 3.School of MedicineBelgradeSerbia

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